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| 2. |
- Dhiman, Kunal, et al.
(författare)
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Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer's disease.
- 2020
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- This study assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) in Alzheimer's disease (AD) diagnosis, its association with amyloid and tau pathology, as well as its potential to predict brain atrophy, cognition, and amyloid accumulation.CSF NfL concentration was measured in 221 participants from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).CSF NfL levels as well as NfL/amyloid β (Aβ42) were significantly elevated in AD compared to healthy controls (HC; P < .001), and in mild cognitive impairment (MCI) compared to HC (P = .008 NfL; P < .001 NfL/Aβ42). CSF NfL and NfL/Aβ42 differentiated AD from HC with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.84 and 0.90, respectively. CSF NfL and NfL/Aβ42 predicted cortical amyloid load, brain atrophy, and cognition.CSF NfL is a biomarker of neurodegeneration, correlating with cognitive impairment and brain neuropathology.
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| 3. |
- Gorbach, Tetiana, 1991-, et al.
(författare)
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Longitudinal association between hippocampus atrophy and episodic-memory decline in non-demented APOE ε4 carriers
- 2020
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Ingår i: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. - : John Wiley & Sons. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic-memory decline in non-demented individuals remains unclear.Methods: We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium.Results: The change-change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non-carriers: N = 467, r = 0.073,P = .117). The linear relationship was significantly steeper for the carriers [t(629) =2.4, P = .013]. A similar trend toward a stronger change-change relation for carriers was seen in a subsample with more than two assessments.Discussion: These findings provide evidence for a difference in hippocampus-memory association between ε4 carriers and non-carriers, thus highlighting how genetic factors modulate the translation of the AD-related pathophysiological cascade into cognitive deficits.
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| 4. |
- Hansson, Oskar, et al.
(författare)
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Pre-analytical protocol for measuring Alzheimer's disease biomarkers in fresh CSF
- 2020
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We aimed to establish a standardized, routine-use pre-analytical protocol for measuring Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF). Methods: The effect of pre-analytical factors (sample collection/handling/storage/transportation) on biomarker levels was assessed using freshly collected CSF. Tube type/sterilization was assessed using previously frozen samples. A low-bind false-bottom tube (FBT, Sarstedt) was used for all experiments, except tube types/sterilization experiments. Biomarkers were measured using Elecsys CSF assays. Results: Amyloid beta (Aβ)1-42 levels varied by tube type, using a low-bind FBT reduced variation. Aβ1-42 levels were higher with no mixing versus roller/inversion mixing. Aβ1-42 levels were lower with horizontal versus upright transportation; this was resolved by maximal tube filling and storage at 2°C to 8°C. Aβ1-40 levels were less strongly affected. Phospho-tau and total-tau levels were largely unaffected. Discussion: We propose an easy-to-use, standardized, routine-use pre-analytical protocol, using low-bind FBTs, for measuring AD CSF biomarkers in clinical practice.
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| 5. |
- Keshavan, Ashvini, et al.
(författare)
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Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays.
- 2020
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on the fully automated Lumipulse platform with pre-symptomatic Alzheimer's disease (AD) pathology on amyloid positron emission tomography (PET).In 72 individuals from the Insight 46 study, CSF Aβ40, Aβ42, total tau (t-tau), and phosphorylated tau at site 181 (p-tau181) were measured using Lumipulse, INNOTEST, and Meso Scale Discovery (MSD) assays, and inter-platform Pearson correlations were derived. Logistic regressions and receiver-operating characteristic analysis generated CSF cut-points optimizing concordance with 18F-florbetapir amyloid PET status (n=63).Measurements of CSF Aβ, p-tau181, and their ratios correlated well across platforms (r 0.84-.94, P<.0001); those of t-tau and t-tau/Aβ42 correlated moderately (r 0.57-0.79, P<.0001). The best concordance with amyloid PET (100% sensitivity and 94% specificity) was afforded by cut-points of 0.110 for Lumipulse Aβ42/Aβ40, 0.087 for MSD Aβ42/Aβ40, and 25.3 for Lumipulse Aβ42/p-tau181.The Lumipulse platform provides comparable sensitivity and specificity to established CSF immunoassays in identifying pre-symptomatic AD pathology.
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| 6. |
- Luo, Jing, et al.
(författare)
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Dementia risk in women higher in same-sex than opposite-sex twins
- 2020
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Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : John Wiley & Sons. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionHormones may be one possible mechanism underlying sex differences in dementia incidence. We examined whether presumed differential prenatal hormone milieu is related to dementia risk by comparing dementia rates in same- and opposite-sex dizygotic twin pairs in male and female twins.MethodsThe sample comprised 43,254 individuals from dizygotic twin pairs aged 60 and older from the Swedish Twin Registry. Survival analyses were conducted separately for females and males.ResultsFemale twins from opposite-sex pairs had significantly lower dementia risk than female twins from same-sex pairs, but the differences emerged only after age 70 (hazard ratio = 0.64, P = 0.004). Results were not explained by postnatal risk factors for dementia, and no interaction between twin type and apolipoprotein E (APOE) epsilon 4 was found. Male twins from same-sex versus opposite-sex pairs did not differ significantly.DiscussionThe results suggest that relatively masculine prenatal hormone milieus correlate with lower dementia risk in females.
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| 7. |
- Nyberg, Lars, 1966-, et al.
(författare)
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Elevated plasma neurofilament light in aging reflects brain white-matter alterations but does not predict cognitive decline or Alzheimer's disease
- 2020
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionWe investigated neurofilament light (NFL) accumulation in normal aging as well as in preclinical and clinical Alzheimer's disease (AD) and assessed individual differences in NFL load in relation to cognition and brain white-matter integrity. MethodsWe analyzed longitudinal data covering 30 years (1988-2017). Cognitive testing was done up to six times. Plasma NFL was quantified for controls and 142 cases who developed AD over time, and longitudinal changes in NFL were quantified for 100 individuals with three brain-imaging sessions. ResultsLongitudinal analyses revealed age-related NFL increases with marked variability. AD cases had elevated NFL levels, while no significant group differences were seen in the preclinical phase. Variability in NFL levels showed non-significant correlations with cognition but was associated with brain white matter. DiscussionOur findings suggest that elevated blood NFL, likely reflecting brain white-matter alterations, characterizes clinical AD, while NFL levels do not predict age-related cognitive impairment or impending AD.
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| 8. |
- Raket, Lars Lau, et al.
(författare)
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Utility of plasma neurofilament light and total tau for clinical trials in Alzheimer's disease
- 2020
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Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several blood-based biomarkers are associated with neuronal injury, but their utility in interventional clinical trials is unclear. This study retrospectively evaluated the utility of plasma neurofilament light (NfL) and total tau (t-tau) in an 18-month trial in mild Alzheimer's disease (AD). Methods: Correlation and conditional independence analyses and Gaussian graphical models were used to investigate cross-sectional and longitudinal relations between NfL, t-tau, and clinical scales. Results: NfL had a stronger association than t-tau with clinical scales; t-tau did not hold additional information to that given by NfL (P > 0.05 at all time points). NfL held independent information about shorter-term (3- to 6-month) progression beyond patient age and clinical scores. However, no meaningful gain in power was found when adjusting a longitudinal analysis of cognitive scores for baseline NfL. Discussion: Plasma NfL is superior to t-tau in mild AD. The ability of NfL to detect changes before clinical manifestations makes it a promising biomarker of drug response in trials of disease-modifying drugs.
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| 10. |
- Wang, Pei-Ning, et al.
(författare)
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Plasma pyroglutamate-modified amyloid beta differentiates amyloid pathology.
- 2020
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Ingår i: Alzheimer's & dementia (Amsterdam, Netherlands). - : Wiley. - 2352-8729. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Pyroglutamate-modified amyloid β (AβpE3) could be a biomarker for Aβ plaque pathology in the brain. An ultra-high-sensitive assay is needed for detecting AβpE3-40.Immunomagnetic reduction was used for quantification of AβpE3-40 in plasma from 46 participants. The concentrations of AβpE3-40 of these subjects were compared with 18F-florbetapir positron emission tomography (PET) images.AβpE3-40 concentration was 44.1 ± 28.2fg/mL in PET- (n = 28) and 91.6 ± 54.6fg/mL in PET+ (n = 18; P < .05). The cutoff value of AβpE3-40 for discriminating PET- from PET+ was 55.5fg/mL, resulting in a sensitivity of 83.3%, a specificity of 71.4%. The concentration of AβpE3-40 showed a moderate correlation (r = 0.437) with PET standardized uptake value ratio.We did not enroll pre-clinical AD subject with normal cognition but Aβ PET+. It would be an important issue to explore the feasibility of using AβpE3-40 for screening pre-clinical subjects.These results reveal the feasibility of detecting Aβ pathology using quantification of a plaque-derived Aβ molecule in plasma.
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