| 1. |
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| 2. |
- Bellaver, B., et al.
(författare)
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Astrocyte reactivity influences amyloid-beta effects on tau pathology in preclinical Alzheimer's disease
- 2023
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Ingår i: Nature Medicine. - 1078-8956. ; 29:7
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Tidskriftsartikel (refereegranskat)abstract
- Cross-sectional and longitudinal analyses of tau pathology in preclinical Alzheimer's disease reveal that tau tangles accumulate as a function of amyloid-beta burden only in individuals positive for an astrocyte reactivity biomarker. An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-beta (A beta)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash A beta effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of A beta with tau phosphorylation in CU individuals. We found that A beta was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast(+)). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of A beta only in CU Ast(+) individuals. Our findings suggest astrocyte reactivity as an important upstream event linking A beta with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
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| 3. |
- Benedet, Andréa L., et al.
(författare)
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Plasma neurofilament light associates with Alzheimer's disease metabolic decline in amyloid-positive individuals
- 2019
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 11, s. 679-689
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Neurofilament light chain (NfL) is a promising blood biomarker to detect neurodegeneration in Alzheimer's disease (AD) and other brain disorders. However, there are limited reports of how longitudinal NfL relates to imaging biomarkers. We herein investigated the relationship between blood NfL and brain metabolism in AD. Methods: Voxelwise regression models tested the cross-sectional association between [18F]fluorodeoxyglucose ([18F]FDG) and both plasma and cerebrospinal fluid NfL in cognitively impaired and unimpaired subjects. Linear mixed models were also used to test the longitudinal association between NfL and [18F]FDG in amyloid positive (Aβ+) and negative (Aβ−) subjects. Results: Higher concentrations of plasma and cerebrospinal fluid NfL were associated with reduced [18F]FDG uptake in correspondent brain regions. In Aβ+ participants, NfL associates with hypometabolism in AD-vulnerable regions. Longitudinal changes in the association [18F]FDG-NfL were confined to cognitively impaired Aβ+ individuals. Discussion: These findings indicate that plasma NfL is a proxy for neurodegeneration in AD-related regions in Aβ+ subjects.
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| 4. |
- Ashton, Nicholas J., et al.
(författare)
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Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease
- 2022
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Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 76
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Tidskriftsartikel (refereegranskat)abstract
- Background: Phosphorylated tau (p-tau) epitopes in cerebrospinal fluid (CSF) are accurate biomarkers for a pathological and clinical diagnosis of Alzheimer's disease (AD) and are seen to be increased in preclinical stage of the disease. However, it is unknown if these increases transpire earlier, prior to amyloid-beta (Aβ) positivity as determined by position emission tomography (PET), and if an ordinal sequence of p-tau epitopes occurs at this incipient phase Methods: We measured CSF concentrations of p-tau181, p-tau217 and p-tau231 in 171 participants across the AD continuum who had undergone Aβ ([18F]AZD4694) and tau ([18F]MK6240) position emission tomography (PET) and clinical assessment Findings: All CSF p-tau biomarkers were accurate predictors of cognitive impairment but CSF p-tau217 demonstrated the largest fold-changes in AD patients in comparison to non-AD dementias and cognitively unimpaired individuals. CSF p-tau231 and p-tau217 predicted Aβ and tau to a similar degree but p-tau231 attained abnormal levels first. P-tau231 was sensitive to the earliest changes of Aβ in the medial orbitofrontal, precuneus and posterior cingulate before global Aβ PET positivity was reached Interpretation: We demonstrate that CSF p-tau231 increases early in development of AD pathology and is a principal candidate for detecting incipient Aβ pathology for therapeutic trial application Funding: Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Weston Brain Institute, Brain Canada Foundation, the Fonds de Recherche du Québec. © 2022
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| 5. |
- Bellaver, B., et al.
(författare)
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Blood-brain barrier integrity impacts the use of plasma amyloid-beta as a proxy of brain amyloid-beta pathology
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:9, s. 3815-3825
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION Amyloid-beta (A beta) and tau can be quantified in blood. However, biological factors can influence the levels of brain-derived proteins in the blood. The blood-brain barrier (BBB) regulates protein transport between cerebrospinal fluid (CSF) and blood. BBB altered permeability might affect the relationship between brain and blood biomarkers.METHODS We assessed 224 participants in research (TRIAD, n = 96) and clinical (BIODEGMAR, n = 128) cohorts with plasma and CSF/positron emission tomography A beta, p-tau, and albumin measures.RESULTS Plasma A beta(42/40) better identified CSF A beta(42/40) and A beta-PET positivity in individuals with high BBB permeability. An interaction between plasma A beta(42/40) and BBB permeability on CSF A beta(42/40) was observed. Voxel-wise models estimated that the association of positron emission tomography (PET), with plasma A beta was most affected by BBB permeability in AD-related brain regions. BBB permeability did not significantly impact the relationship between brain and plasma p-tau levels.DISCUSSION These findings suggest that BBB integrity may influence the performance of plasma A beta, but not p-tau, biomarkers in research and clinical settings.
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| 6. |
- Brum, Wagner S., et al.
(författare)
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A three-range approach enhances the prognostic utility of CSF biomarkers in Alzheimer's disease.
- 2022
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Ingår i: Alzheimer's & dementia (New York, N. Y.). - : Wiley. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease consensus recommends biomarker dichotomization, a practice with well-described clinical strengths and methodological limitations. Although neuroimaging studies have explored alternative biomarker interpretation strategies, a formally defined three-range approach and its prognostic impact remains under-explored for cerebrospinal fluid (CSF) biomarkers .With two-graph receiver-operating characteristics based on different reference schemes, we derived three-range cut-points for CSF Elecsys biomarkers. According to baseline CSF status, we assessed the prognostic utility of this in predicting risk of clinical progression and longitudinal trajectories of cognitive decline and amyloid-beta (Aβ) positron emission tomography (PET) accumulation in non-demented individuals (Alzheimer's Disease Neuroimaging Initiative [ADNI]; n=1246). In all analyses, we compared herein-derived three-range CSF cut-points to previously described binary ones.In our main longitudinal analyses, we highlight CSF p-tau181/Aβ1-42 three-range cut-points derived based on the cognitively normal Aβ-PET negative versus dementia Aβ-PET positive reference scheme for best depicting a prognostically relevant biomarker abnormality range. Longitudinally, our approach revealed a divergent intermediate cognitive trajectory undetected by dichotomization and a clearly abnormal group at higher risk for cognitive decline, with power analyses suggesting the latter group as potential trial enrichment candidates. Furthermore, we demonstrate that individuals with intermediate-range CSF status have similar rates of Aβ deposition to those in the clearly abnormal group.The proposed approach can refine clinico-biological prognostic assessment and potentially enhance trial recruitment, as it captures faster biomarker-related cognitive decline in comparison to binary cut-points. Although this approach has implications for trial recruitment and observational studies, further discussion is needed regarding clinical practice applications.
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| 7. |
- De Bastiani, Marco Antônio, et al.
(författare)
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Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies.
- 2023
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 1090-2139 .- 0889-1591. ; 110, s. 175-184
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Tidskriftsartikel (refereegranskat)abstract
- In Alzheimer's disease clinical research, glial fibrillary acidic protein (GFAP) released/leaked into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathologies. The molecular underpinnings behind this specificity are little explored. Here we investigated biomarker and transcriptomic associations of hippocampal GFAP-positive astrocytes with Aβ and tau pathologies in humans and mouse models.We studied 90 individuals with plasma GFAP, Aβ- and Tau-PET to investigate the association between biomarkers. Then, transcriptomic analysis in hippocampal GFAP-positive astrocytes isolated from mouse models presenting Aβ (PS2APP) or tau (P301S) pathologies was conducted to explore differentially expressed genes (DEGs), Gene Ontology terms, and protein-protein interaction networks associated with each phenotype.In humans, we found that plasma GFAP associates with Aβ but not tau pathology. Unveiling the unique nature of hippocampal GFAP-positive astrocytic responses to Aβ or tau pathologies, mouse transcriptomics showed scarce overlap of DEGs between the Aβ. and tau mouse models. While Aβ GFAP-positive astrocytes were overrepresented with DEGs associated with proteostasis and exocytosis-related processes, tau hippocampal GFAP-positive astrocytes presented greater abnormalities in functions related to DNA/RNA processing and cytoskeleton dynamics.Our results offer insights into Aβ- and tau-driven specific signatures in hippocampal GFAP-positive astrocytes. Characterizing how different underlying pathologies distinctly influence astrocyte responses is critical for the biological interpretation of astrocyte biomarkers and suggests the need to develop context-specific astrocyte targets to study AD.This study was supported by Instituto Serrapilheira, Alzheimer's Association, CAPES, CNPq and FAPERGS.
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| 8. |
- Fernandes, Susana C. M., et al.
(författare)
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Transparent chitosan films reinforced with a high content of nanofibrillated cellulose
- 2010
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 81:2, s. 394-401
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the preparation and characterization of nanocomposite films based on different chitosan matrices and nanofibrillated cellulose (NFC) for the purpose of improving strength properties. The nanocomposite films were prepared by a simple procedure of casting a water-based suspension of chitosan and NFC, and were characterized by several techniques: namely SEM, X-ray diffraction, visible spectrophotometry, TGA, tensile and dynamic-mechanical analysis. The films obtained were shown to be highly transparent (transmittance varying between 90 and 20% depending on the type of chitosan and NFC content), flexible, displayed better mechanical properties, with a maximum increment on the Young's modulus of 78% and 150% for high molecular weight (HCH) and water-soluble high molecular weight (WSHCH) filled chitosans, respectively; and of 200% and 320% for low molecular weight (LCH) and water-soluble filled (WSLCH) chitosans, respectively. The filled films also showed increased thermal stability, with, for example, an increase in the initial degradation temperature (Td(i)) from 227 degrees C in the unfilled LCH film up to 271 degrees C in filled LCHNFC50% nanocomposite films, and a maximum degradation temperature (Tdi) raising from 304 degrees C to 313 degrees C for the same materials.
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| 9. |
- Ferrari-Souza, J. P., et al.
(författare)
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APOEε4 associates with microglial activation independently of Aβ plaques and tau tangles
- 2023
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Ingår i: Science Advances. - 2375-2548. ; 9:14
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest that the apolipoprotein E epsilon 4 (APOE epsilon 4) allele is a culprit of early microglial activation in Alzheimer's disease (AD). Here, we tested the association between APOE epsilon 4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomog-raphy for amyloid-beta (A beta; [18F]AZD4694), tau ([18F]MK6240), and microglial activation ([11C]PBR28). We found that APOE epsilon 4 carriers presented increased microglial activation relative to noncarriers in early Braak stage regions within the medial temporal cortex accounting for A beta and tau deposition. Furthermore, microglial acti-vation mediated the A beta-independent effects of APOE epsilon 4 on tau accumulation, which was further associated with neurodegeneration and clinical impairment. The physiological distribution of APOE mRNA expression predicted the patterns of APOE epsilon 4-related microglial activation in our population, suggesting that APOE gene expression may regulate the local vulnerability to neuroinflammation. Our results support that the APOE epsilon 4 genotype exerts A beta-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition.
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| 10. |
- Ferrari-Souza, J. P., et al.
(författare)
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APOEε4 potentiates amyloid β effects on longitudinal tau pathology
- 2023
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Ingår i: Nature Aging. - 2662-8465. ; 3:10
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms by which the apolipoprotein E epsilon 4 (APOE epsilon 4) allele influences the pathophysiological progression of Alzheimer's disease (AD) are poorly understood. Here we tested the association of APOE epsilon 4 carriership and amyloid-beta (A beta) burden with longitudinal tau pathology. We longitudinally assessed 94 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for A beta ([F-18]AZD4694) and tau ([F-18]MK-6240) at baseline, as well as a 2-year follow-up tau-PET scan. We found that APOE epsilon 4 carriership potentiates A beta effects on longitudinal tau accumulation over 2 years. The APOE epsilon 4-potentiated A beta effects on tau-PET burden were mediated by longitudinal plasma phosphorylated tau at threonine 217 (p-tau217(+)) increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results suggest that the APOE epsilon 4 allele plays a key role in A beta downstream effects on the aggregation of phosphorylated tau in the living human brain.
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| 11. |
- Ferrari-Souza, J. P., et al.
(författare)
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Astrocyte biomarker signatures of amyloid-beta and tau pathologies in Alzheimer's disease
- 2022
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27:11, s. 4781-4789
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-beta (A beta) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for A beta ([F-18]AZD4694) and tau ([F-18]MK-6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated A beta-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not A beta-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of A beta and tau, respectively, on hippocampal atrophy, which was further associated with cognitive impairment. Our results suggest the existence of distinct astrocyte biomarker signatures in response to brain A beta and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.
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| 12. |
- Ferrari-Souza, Joao Pedro, et al.
(författare)
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Vascular risk burden is a key player in the early progression of Alzheimer's disease
- 2024
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Ingår i: NEUROBIOLOGY OF AGING. - 0197-4580 .- 1558-1497. ; 136, s. 88-98
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Tidskriftsartikel (refereegranskat)abstract
- Understanding whether vascular risk factors (VRFs) synergistically potentiate Alzheimer's disease (AD) progression is important in the context of emerging treatments for preclinical AD. In a group of 503 cognitively unimpaired individuals, we tested whether VRF burden interacts with AD pathophysiology to accelerate neurodegeneration and cognitive decline. Baseline VRF burden was calculated considering medical data and AD pathophysiology was assessed based on cerebrospinal fluid (CSF) amyloid-beta 1-42 (A beta 1-42) and tau phosphorylated at threonine 181 (p-tau181). Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. The mean (SD) age of participants was 72.9 (6.1) years, and 220 (43.7%) were men. Linear mixed-effects models revealed that an elevated VRF burden synergistically interacted with AD pathophysiology to drive longitudinal plasma NfL increase and cognitive decline. Additionally, VRF burden was not associated with CSF A beta 1-42or p-tau181 changes over time. Our results suggest that VRF burden and AD pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive deterioration. In preclinical stages, the combination of therapies targeting VRFs and AD pathophysiology might potentiate treatment outcomes.
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| 13. |
- Ferreira, Pamela C. L., et al.
(författare)
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Endocannabinoid System Biomarkers in Alzheimer's Disease
- 2023
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Ingår i: CANNABIS AND CANNABINOID RESEARCH. - : Mary Ann Liebert Inc. - 2578-5125 .- 2378-8763. ; 8:1, s. 77-91
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alterations in the endocannabinoid system (ES) have been described in Alzheimer's disease (AD) pathophysiology. In the past years, multiple ES biomarkers have been developed, promising to advance our understanding of ES changes in AD.Discussion: ES biomarkers, including positron emission tomography with cannabinoid receptors tracers and biofluid-based endocannabinoids, are associated with AD disease progression and pathological features.Conclusion: Although not specific enough for AD diagnosis, ES biomarkers hold promise for prognosis, drug-target engagement, and a better understanding of the disease. Here, we summarize currently available ES biomarker findings and discuss their potential applications in the AD research field.
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| 14. |
- Ferreira, P. C. L., et al.
(författare)
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Plasma p-tau231 and p-tau217 inform on tau tangles aggregation in cognitively impaired individuals
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:10, s. 4463-4474
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONPhosphorylated tau (p-tau) biomarkers have been recently proposed to represent brain amyloid-& beta; (A & beta;) pathology. Here, we evaluated the plasma biomarkers' contribution beyond the information provided by demographics (age and sex) to identify A & beta; and tau pathologies in individuals segregated as cognitively unimpaired (CU) and impaired (CI). METHODSWe assessed 138 CU and 87 CI with available plasma p-tau231, 217(+), and 181, A & beta;42/40, GFAP and A & beta;- and tau-PET. RESULTSIn CU, only plasma p-tau231 and p-tau217(+) significantly improved the performance of the demographics in detecting A & beta;-PET positivity, while no plasma biomarker provided additional information to identify tau-PET positivity. In CI, p-tau217(+) and GFAP significantly contributed to demographics to identify both A & beta;-PET and tau-PET positivity, while p-tau231 only provided additional information to identify tau-PET positivity. DISCUSSIONOur results support plasma p-tau231 and p-tau217(+) as state markers of early A & beta; deposition, but in later disease stages they inform on tau tangle accumulation. HighlightsIt is still unclear how much plasma biomarkers contribute to identification of AD pathology across the AD spectrum beyond the information already provided by demographics (age + sex).Plasma p-tau231 and p-tau217(+) contribute to demographic information to identify brain A & beta; pathology in preclinical AD.In CI individuals, plasma p-tau231 contributes to age and sex to inform on the accumulation of tau tangles, while p-tau217(+) and GFAP inform on both A & beta; deposition and tau pathology.
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| 15. |
- Ferreira, P. C. L., et al.
(författare)
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Potential Utility of Plasma P-Tau and Neurofilament Light Chain as Surrogate Biomarkers for Preventive Clinical Trials
- 2023
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Ingår i: NEUROLOGY. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 101:1, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo test the utility of longitudinal changes in plasma phosphorylated tau 181 (p-tau181) and neurofilament light chain (NfL) as surrogate markers for clinical trials targeting cognitively unimpaired (CU) populations.MethodsWe estimated the sample size needed to test a 25% drug effect with 80% of power at a 0.05 level on reducing changes in plasma markers in CU participants from Alzheimer's Disease Neuroimaging Initiative database.ResultsWe included 257 CU individuals (45.5% males; mean age = 73 [6] years; 32% & beta;-amyloid [A & beta;] positive). Changes in plasma NfL were associated with age, whereas changes in plasma p-tau181 with progression to amnestic mild cognitive impairment. Clinical trials using p-tau181 and NfL would require 85% and 63% smaller sample sizes, respectively, for a 24-month than a 12-month follow-up. A population enrichment strategy using intermediate levels of A & beta; PET (Centiloid 20-40) further reduced the sample size of the 24-month clinical trial using p-tau181 (73%) and NfL (59%) as a surrogate.DiscussionPlasma p-tau181/NfL can potentially be used to monitor large-scale population interventions in CU individuals. The enrollment of CU with intermediate A & beta; levels constitutes the alternative with the largest effect size and most cost-effective for trials testing drug effect on changes in plasma p-tau181 and NfL.
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| 16. |
- Gonzalez-Ortiz, Fernando, et al.
(författare)
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A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease.
- 2024
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279. ; 20:2, s. 1239-1249
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Tidskriftsartikel (refereegranskat)abstract
- Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changesand those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p-tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.We employed a novel p-tau217 immunoassay (University of Gothenburg [UGOT] p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (Barcelonaβeta Brain Research Center's Alzheimer's At-Risk Cohort [β-AARC]).UGOT p-tau217 showed high accuracy (area under the curve [AUC]=0.80-0.91) identifying amyloid beta (Aβ) pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC=0.91).UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
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| 17. |
- Gonzalez-Ortiz, Fernando, et al.
(författare)
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A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer's disease.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Detection of Alzheimer's disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.We employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (β-AARC).UGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aβ pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC= 0.91).UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.
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| 18. |
- Lantero Rodriguez, Juan, et al.
(författare)
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Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden
- 2023
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 19:12, s. 5343-5354
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONFluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed. METHODSWe measured cerebrospinal fluid (CSF) and plasma concentrations of N-terminal tau fragments (NTA-tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (A beta) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments. RESULTSCSF and plasma NTA-tau concentrations were specifically increased in cognitively impaired A beta-positive groups. CSF and plasma NTA-tau concentrations displayed stronger correlations with tau PET than with A beta PET and MRI, both in global uptake and at the voxel level. Regression models demonstrated that both CSF and plasma NTA-tau are preferentially associated with tau pathology. Moreover, plasma NTA-tau was associated with longitudinal tau PET accumulation across the aging and Alzheimer's disease (AD) spectrum. DISCUSSIONNTA-tau is a biomarker closely associated with in vivo tau deposition in the AD continuum and has potential as a tau tangle biomarker in clinical settings and trials. HIGHLIGHTSAn assay for detecting N-terminal tau fragments (NTA-tau) in plasma and CSF was evaluated.NTA-tau is more closely associated with tau PET than amyloid PET or neurodegeneration.NTA-tau can successfully track in vivo tau deposition across the AD continuum.Plasma NTA-tau increased over time only in cognitively impaired amyloid-beta positive individuals.
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| 19. |
- Leffa, D. T., et al.
(författare)
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Genetic risk for attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer's disease pathophysiology in cognitively unimpaired older adults
- 2023
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 28:3, s. 1248-1255
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Tidskriftsartikel (refereegranskat)abstract
- Attention-deficit/hyperactivity disorder (ADHD) persists in older age and is postulated as a risk factor for cognitive impairment and Alzheimer's Disease (AD). However, these findings rely primarily on electronic health records and can present biased estimates of disease prevalence. An obstacle to investigating age-related cognitive decline in ADHD is the absence of large-scale studies following patients with ADHD into older age. Alternatively, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults. We calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years). These individuals had baseline amyloid-beta (A beta) positron emission tomography, longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181 (p-tau(181)), magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers. Higher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain A beta deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau(181) levels and frontoparietal atrophy in CU A beta-positive individuals. Our results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology. Findings were mostly observed in A beta-positive individuals, suggesting that the genetic liability for ADHD increases susceptibility to the harmful effects of A beta pathology.
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| 20. |
- Lessa Benedet, Andréa, et al.
(författare)
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Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum
- 2021
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:12, s. 1471-1483
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Tidskriftsartikel (refereegranskat)abstract
- Question What are the levels of plasma glial fibrillary acidic protein (GFAP) throughout the Alzheimer disease (AD) continuum, and how do they compare with the levels of cerebrospinal fluid (CSF) GFAP? Findings In this cross-sectional study, plasma GFAP levels were elevated in the preclinical and symptomatic stages of AD, with levels higher than those of CSF GFAP. Plasma GFAP had a higher accuracy than CSF GFAP to discriminate between amyloid-beta (A beta)-positive and A beta-negative individuals, also at the preclinical stage. Meaning This study suggests that plasma GFAP is a sensitive biomarker that significantly outperforms CSF GFAP in indicating A beta pathology in the early stages of AD. Importance Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CSF GFAP. Objective To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP. Design, Setting, and Participants This observational, cross-sectional study collected data from July 29, 2014, to January 31, 2020, from 3 centers. The Translational Biomarkers in Aging and Dementia (TRIAD) cohort (Montreal, Canada) included individuals in the entire AD continuum. Results were confirmed in the Alzheimer's and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisiere cohort (Paris, France), which included individuals with symptomatic AD. Main Outcomes and Measures Plasma and CSF GFAP levels measured with a Simoa assay were the main outcome. Other measurements included levels of CSF amyloid-beta 42/40 (A beta 42/40), phosphorylated tau181 (p-tau181), neurofilament light (NfL), Chitinase-3-like protein 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and levels of plasma p-tau181 and NfL. Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD. Results A total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisiere participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included. Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) A beta-negative individuals (TRIAD: A beta-negative mean [SD], 185.1 [93.5] pg/mL, A beta-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: A beta-negative mean [SD], 121.9 [42.4] pg/mL, A beta-positive mean [SD], 169.9 [78.5] pg/mL). Plasma GFAP levels were also higher among individuals in symptomatic stages of the AD continuum (TRIAD: CU A beta-positive mean [SD], 285.0 [142.6] pg/mL, mild cognitive impairment [MCI] A beta-positive mean [SD], 332.5 [153.6] pg/mL; AD mean [SD], 388.1 [152.8] pg/mL vs CU A beta-negative mean [SD], 185.1 [93.5] pg/mL; Paris: MCI A beta-positive, mean [SD], 368.6 [158.5] pg/mL; AD dementia, mean [SD], 376.4 [179.6] pg/mL vs CU A beta-negative mean [SD], 161.2 [67.1] pg/mL). Plasma GFAP magnitude changes were consistently higher than those of CSF GFAP. Plasma GFAP more accurately discriminated A beta-positive from A beta-negative individuals than CSF GFAP (area under the curve for plasma GFAP, 0.69-0.86; area under the curve for CSF GFAP, 0.59-0.76). Moreover, plasma GFAP levels were positively associated with tau pathology only among individuals with concomitant A beta pathology. Conclusions and Relevance This study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and A beta pathology even among individuals in the early stages of AD. This cross-sectional cohort study evaluates plasma glial fibrillary acidic protein levels throughout the entire Alzheimer disease continuum, from preclinical Alzheimer disease to Alzheimer disease dementia, compared with cerebrospinal fluid glial fibrillary acidic protein.
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| 21. |
- Lessa Benedet, Andréa, et al.
(författare)
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Stage-specific links between plasma neurofilament light and imaging biomarkers of Alzheimer's disease
- 2020
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:12, s. 3793-3804
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light (NfL) is a marker of neuroaxonal injury, a prominent feature of Alzheimer's disease. It remains uncertain, however, how it relates to amyloid and tau pathology or neurodegeneration across the Alzheimer's disease continuum. The aim of this study was to investigate how plasma NfL relates to amyloid and tau PET and MRI measures of brain atrophy in participants with and without cognitive impairment. We retrospectively examined the association between plasma NfL and MRI measures of grey/white matter volumes in the Alzheimer's Disease Neuroimaging Initiative [ADNI: n = 1149; 382 cognitively unimpaired control subjects and 767 cognitively impaired participants (mild cognitive impairment n = 420, Alzheimer's disease dementia n = 347)]. Longitudinal plasma NfL was measured using single molecule array (Simoa) technology. Cross-sectional associations between plasma NfL and PET amyloid and tau measures were independently assessed in two cohorts: ADNI [n = 198; 110 cognitively unimpaired, 88 cognitively impaired (MCI n = 67, Alzheimer's disease dementia n = 21), data accessed October 2018]; and Translational Biomarkers in Aging and Dementia [TRIAD, n = 116; 74 cognitively unimpaired, 42 cognitively impaired (MCI n = 16, Alzheimer's disease dementia n = 26), data obtained November 2017 to January 2019]. Associations between plasma NfL and imaging-derived measures were examined voxel-wise using linear regression (cross-sectional) and linear mixed effect models (longitudinal). Cross-sectional analyses in both cohorts showed that plasma NfL was associated with PET findings in brain regions typically affected by Alzheimer's disease; associations were specific to amyloid PET in cognitively unimpaired and tau PET in cognitively impaired (P < 0.05). Longitudinal analyses showed that NfL levels were associated with grey/white matter volume loss; grey matter atrophy in cognitively unimpaired was specific to APOE ϵ4 carriers (P < 0.05). These findings suggest that plasma NfL increases in response to amyloid-related neuronal injury in preclinical stages of Alzheimer's disease, but is related to tau-mediated neurodegeneration in symptomatic patients. As such, plasma NfL may a useful measure to monitor effects in disease-modifying drug trials.
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| 22. |
- Moller, Anders Pape, et al.
(författare)
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Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design
- 2014
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:4, s. 353-362
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Tidskriftsartikel (refereegranskat)abstract
- Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
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| 23. |
- Rusz, Jan, et al.
(författare)
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Probing the electronic structure of pure and doped CeMIn5 (M=Co,Rh,Ir) crystals with nuclear quadrupolar resonance
- 2008
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 77:24, s. 245124-
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Tidskriftsartikel (refereegranskat)abstract
- We report calculations of the electric-field gradients (EFGs) in pure and doped CeMIn5 (M=Co, Rh, and Ir) compounds and compare with experiment. The degree to which the Ce 4f electron is localized is treated within various models: the local-density approximation, generalized gradient approximation (GGA), GGA+U, and 4f-core approaches. We find that there is a correlation between the observed EFG and whether the 4f electron participates in the band formation or not. We also find that the EFG evolves linearly with Sn doping in CeRhIn5, suggesting the electronic structure is modified by doping. In contrast, the observed EFG in CeCoIn5 doped with Cd changes little with doping. These results indicate that nuclear quadrupolar resonance is a sensitive probe of electronic structure.
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| 24. |
- Schaffer Aguzzoli, Cristiano, et al.
(författare)
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Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease
- 2023
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Ingår i: JAMA network open. - 2574-3805. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms. Objective: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum. Design, Setting, and Participants: This cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions. Main Outcomes and Measures: All individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET). Results: Of the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β=7.37; 95% CI, 1.34-13.41; P=.01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β=6.86; 95% CI, 1.77-11.95; P=.008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β=5.72; 95% CI, 0.33-11.10; P=.03). Conclusions and Relevance: In this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.
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| 25. |
- Therriault, Joseph, et al.
(författare)
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Association of Phosphorylated Tau Biomarkers With Amyloid Positron Emission Tomography vs Tau Positron Emission Tomography.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 80:2, s. 188-99
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Tidskriftsartikel (refereegranskat)abstract
- The recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies of Alzheimer disease (AD): amyloid-β plaques and tau neurofibrillary tangles.To determine whether cerebrospinal fluid (CSF) and plasma p-tau biomarkers preferentially reflect cerebral β-amyloidosis or neurofibrillary tangle aggregation measured with positron emission tomography (PET).This was a cross-sectional study of 2 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) study, with data collected between October 2017 and August 2021, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), with data collected between September 2015 and November 2019. TRIAD was a single-center study, and ADNI was a multicenter study. Two independent subsamples were derived from TRIAD. The first TRIAD subsample comprised individuals assessed with CSF p-tau (p-tau181, p-tau217, p-tau231, p-tau235), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. The second TRIAD subsample included individuals assessed with plasma p-tau (p-tau181, p-tau217, p-tau231), [18F]AZD4694 amyloid PET, and [18F]MK6240 tau PET. An independent cohort from ADNI comprised individuals assessed with CSF p-tau181, [18F]florbetapir PET, and [18F]flortaucipir PET. Participants were included based on the availability of p-tau and PET biomarker assessments collected within 9 months of each other. Exclusion criteria were a history of head trauma or magnetic resonance imaging/PET safety contraindications. No participants who met eligibility criteria were excluded.Amyloid PET, tau PET, and CSF and plasma assessments of p-tau measured with single molecule array (Simoa) assay or enzyme-linked immunosorbent assay.Associations between p-tau biomarkers with amyloid PET and tau PET.A total of 609 participants (mean [SD] age, 66.9 [13.6] years; 347 female [57%]; 262 male [43%]) were included in the study. For all 4 phosphorylation sites assessed in CSF, p-tau was significantly more closely associated with amyloid-PET values than tau-PET values (p-tau181 difference, 13%; 95% CI, 3%-22%; P=.006; p-tau217 difference, 11%; 95% CI, 3%-20%; P=.003; p-tau231 difference, 15%; 95% CI, 5%-22%; P<.001; p-tau235 difference, 9%; 95% CI, 1%-19%; P=.02) . These results were replicated with plasma p-tau181 (difference, 11%; 95% CI, 1%-22%; P=.02), p-tau217 (difference, 9%; 95% CI, 1%-19%; P=.02), p-tau231 (difference, 13%; 95% CI, 3%-24%; P=.009), and CSF p-tau181 (difference, 9%; 95% CI, 1%-21%; P=.02) in independent cohorts.Results of this cross-sectional study of 2 observational cohorts suggest that the p-tau abnormality as an early event in AD pathogenesis was associated with amyloid-β accumulation and highlights the need for careful interpretation of p-tau biomarkers in the context of the amyloid/tau/neurodegeneration, or A/T/(N), framework.
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| 26. |
- Therriault, Joseph, et al.
(författare)
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Biomarker-based staging of Alzheimer disease: rationale and clinical applications.
- 2024
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Ingår i: Nature reviews. Neurology. - 1759-4766. ; 20:4, s. 232-244
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Tidskriftsartikel (refereegranskat)abstract
- Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity ofAlzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical decision-making in the era of anti-amyloid therapeutics. We provide a state-of-the-art review of recent biomarker-based AD staging systems and highlight their contributions to the understanding of the natural history of AD. Furthermore, we outline hypothetical frameworks to stage AD severity using more accessible fluid biomarkers. In addition, by applying amyloid PET-based staging to recently published anti-amyloid therapeutic trials, we highlight how biomarker-based disease staging frameworks could illustrate the numerous pathological changes that have already taken place in individuals with mildly symptomatic AD. Finally, we discuss challenges related to the validation and standardization of disease staging and provide a forward-looking perspective on potential clinical applications.
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| 27. |
- Therriault, J., et al.
(författare)
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Staging of Alzheimer?s disease: past, present and future perspectives
- 2022
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Ingår i: Trends in Molecular Medicine. - : Elsevier BV. - 1471-4914. ; 28:9, s. 726-741
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Tidskriftsartikel (refereegranskat)abstract
- For many years Alzheimer's disease (AD) was associated with the dementia stage of the disease, the tail end of a pathophysiological process that lasts approximately two decades. Whereas early disease staging assessments focused on progressive deterioration of clinical functioning, brain imaging with positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarker studies highlighted the long preclinical phase of AD in which a cascade of detectable biological abnormalities precede cognitive decline. The recent pro-liferation of imaging and fluid biomarkers of AD pathophysiology provide an opportunity for the identification of several biological stages in the preclinical phase of AD. We discuss the use of clinical and biomarker information in past, present, and future staging of AD. We highlight potential applications of PET, CSF, and plasma biomarkers for staging AD severity in vivo.
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| 28. |
- Tissot, C., et al.
(författare)
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The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of 18F MK6240 Tau PET in Target Regions
- 2023
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 64:3, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- 6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F] MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stabil-ity of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off -target retention on the longitudinal quantification of [18F]MK6240 in tar-get regions. Methods: We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzhei-mer disease spectrum with longitudinal [18F]MK6240 SUVs and SUV ratios (SUVRs) (mean +/- SD, 2.25 +/- 0.40 y of follow-up). We obtained SUVR from meninges, exhibiting frequent off-target retention with [18F]MK6240. Additionally, we compared tracer uptake between 37 cognitively unimpaired young (CUY) (mean age, 23.41 +/- 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-P-negative and tau-negative, 58.50 +/- 9.01 y) to identify possible nonvisually apparent, age-related signal. Two-tailed t testing and Pearson correlation testing were used to determine the difference between groups and associa-tions between changes in region uptake, respectively. Results: Inferior cerebellar gray matter SUV did not differ on the basis of diagnosis and amyloid-P status, cross-sectionally and over time. [18F]MK6240 uptake significantly differed between CUY and CU adults in the puta-men or pallidum (affecting-75% of the region) and in the Braak II region (affecting-35%). Changes in meningeal and putamen or palli-dum SUVRs did not significantly differ from zero, nor did they vary across diagnostic groups. We did not observe significant correlations between longitudinal changes in age-related or meningeal off-target retention and changes in target regions, whereas changes in all target regions were strongly correlated. Conclusion: Inferior cerebellar gray matter was similar across diagnostic groups cross-sectionally and sta-ble over time and thus was deemed a suitable reference region for quantification. Despite not being visually perceptible, [18F]MK6240 has age-related retention in subcortical regions, at a much lower magnitude but topographically colocalized with significant off-target signal of the first-generation tau tracers. The lack of correlation between changes in age-related or meningeal and target retention suggests little influence of possible off-target signals on longitudinal tracer quantification. Nev-ertheless, the age-related retention in the Braak II region needs to be further investigated. Future postmortem studies should elucidate the source of the newly reported age-related [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification.
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| 29. |
- Tlili, A., et al.
(författare)
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Pollution-induced community tolerance (PICT): towards an ecologically relevant risk assessment of chemicals in aquatic systems
- 2016
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 61:12, s. 2141-2151
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in environmental risk assessment of pollutants is establishing a causal relationship between field exposure and community effects that integrates both structural and functional complexity within ecosystems. Pollution-induced community tolerance (PICT) is a concept that evaluates whether pollutants have exerted a selection pressure on natural communities. PICT detects whether a pollutant has eliminated sensitive species from a community and thereby increased its tolerance. PICT has the potential to link assessments of the ecological and chemical status of ecosystems by providing causal analysis for effect-based monitoring of impacted field sites. Using PICT measurements and microbial community endpoints in environmental assessment schemes could give more ecological relevance to the tools that are now used in environmental risk assessment. Here, we propose practical guidance and a list of research issues that should be further considered to apply the PICT concept in the field.
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| 30. |
- Vaugoyeau, Marie, et al.
(författare)
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Interspecific variation in the relationship between clutch size, laying date and intensity of urbanization in four species of hole-nesting birds
- 2016
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 6:16, s. 5907-5920
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Tidskriftsartikel (refereegranskat)abstract
- The increase in size of human populations in urban and agricultural areas has resulted in considerable habitat conversion globally. Such anthropogenic areas have specific environmental characteristics, which influence the physiology, life history, and population dynamics of plants and animals. For example, the date of bud burst is advanced in urban compared to nearby natural areas. In some birds, breeding success is determined by synchrony between timing of breeding and peak food abundance. Pertinently, caterpillars are an important food source for the nestlings of many bird species, and their abundance is influenced by environmental factors such as temperature and date of bud burst. Higher temperatures and advanced date of bud burst in urban areas could advance peak caterpillar abundance and thus affect breeding phenology of birds. In order to test whether laying date advance and clutch sizes decrease with the intensity of urbanization, we analyzed the timing of breeding and clutch size in relation to intensity of urbanization as a measure of human impact in 199 nest box plots across Europe, North Africa, and the Middle East (i.e., the Western Palearctic) for four species of hole-nesters: blue tits (Cyanistes caeruleus), great tits (Parus major), collared flycatchers (Ficedula albicollis), and pied flycatchers (Ficedula hypoleuca). Meanwhile, we estimated the intensity of urbanization as the density of buildings surrounding study plots measured on orthophotographs. For the four study species, the intensity of urbanization was not correlated with laying date. Clutch size in blue and great tits does not seem affected by the intensity of urbanization, while in collared and pied flycatchers it decreased with increasing intensity of urbanization. This is the first large-scale study showing a species-specific major correlation between intensity of urbanization and the ecology of breeding. The underlying mechanisms for the relationships between life history and urbanization remain to be determined. We propose that effects of food abundance or quality, temperature, noise, pollution, or disturbance by humans may on their own or in combination affect laying date and/or clutch size.
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