| 1. |
- Beckers, Elise, et al.
(författare)
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Microstructural associations between locus coeruleus, cortical, and subcortical regions are modulated by astrocyte reactivity: a 7T MRI adult lifespan study
- 2024
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Ingår i: CEREBRAL CORTEX. - 1047-3211 .- 1460-2199. ; 34:6
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Tidskriftsartikel (refereegranskat)abstract
- The locus coeruleus-norepinephrine system plays a key role in supporting brain health along the lifespan, notably through its modulatory effects on neuroinflammation. Using ultra-high field diffusion magnetic resonance imaging, we examined whether microstructural properties (neurite density index and orientation dispersion index) in the locus coeruleus were related to those in cortical and subcortical regions, and whether this was modulated by plasma glial fibrillary acidic protein levels, as a proxy of astrocyte reactivity. In our cohort of 60 healthy individuals (30 to 85 yr, 50% female), higher glial fibrillary acidic protein correlated with lower neurite density index in frontal cortical regions, the hippocampus, and the amygdala. Furthermore, under higher levels of glial fibrillary acidic protein (above similar to 150 pg/mL for cortical and similar to 145 pg/mL for subcortical regions), lower locus coeruleus orientation dispersion index was associated with lower orientation dispersion index in frontotemporal cortical regions and in subcortical regions. Interestingly, individuals with higher locus coeruleus orientation dispersion index exhibited higher orientation dispersion index in these (sub)cortical regions, despite having higher glial fibrillary acidic protein levels. Together, these results suggest that the interaction between locus coeruleus-norepinephrine cells and astrocytes can signal a detrimental or neuroprotective pathway for brain integrity and support the importance of maintaining locus coeruleus neuronal health in aging and in the prevention of age-related neurodegenerative diseases.
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| 2. |
- Cacciaglia, Raffaele, et al.
(författare)
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APOE-ε4 Shapes the Cerebral Organization in Cognitively Intact Individuals as Reflected by Structural Gray Matter Networks.
- 2020
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Ingår i: Cerebral cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 30:7, s. 4110-4120
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Tidskriftsartikel (refereegranskat)abstract
- Gray matter networks (GMn) provide essential information on the intrinsic organization of the brain and appear to be disrupted in Alzheimer's disease (AD). Apolipoprotein E (APOE)-ε4 represents the major genetic risk factor for AD, yet the association between APOE-ε4 and GMn has remained unexplored. Here, we determine the impact of APOE-ε4 on GMn in a large sample of cognitively unimpaired individuals, which was enriched for the genetic risk of AD. We used independent component analysis to retrieve sources of structural covariance and analyzed APOE group differences within and between networks. Analyses were repeated in a subsample of amyloid-negative subjects. Compared with noncarriers and heterozygotes, APOE-ε4 homozygotes showed increased covariance in one network including primarily right-lateralized, parietal, inferior frontal, as well as inferior and middle temporal regions, which mirrored the formerly described AD-signature. This result was confirmed in a subsample of amyloid-negative individuals. APOE-ε4 carriers showed reduced covariance between two networks encompassing frontal and temporal regions, which constitute preferential target of amyloid deposition. Our data indicate that, in asymptomatic individuals, APOE-ε4 shapes the cerebral organization in a way that recapitulates focal morphometric alterations observed in AD patients, even in absence of amyloid pathology. This suggests that structural vulnerability in neuronal networks associated with APOE-ε4 may be an early event in AD pathogenesis, possibly upstream of amyloid deposition.
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| 3. |
- Cacciaglia, R., et al.
(författare)
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Genotypic effects of APOE-epsilon 4 on resting-state connectivity in cognitively intact individuals support functional brain compensation
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 33:6, s. 2748-60
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Tidskriftsartikel (refereegranskat)abstract
- The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-epsilon 4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the epsilon 4 allele. Yet, no study has assessed APOE-epsilon 4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-epsilon 4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of epsilon 4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-epsilon 4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the epsilon 4-homozygotes. Our data indicate that APOE-epsilon 4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.
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| 4. |
- Canal-Garcia, Anna, et al.
(författare)
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Dynamic multilayer functional connectivity detects preclinical and clinical Alzheimer's disease
- 2024
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Ingår i: CEREBRAL CORTEX. - 1047-3211 .- 1460-2199. ; 34:2
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that patients with Alzheimer's disease present alterations in functional connectivity but previous results have not always been consistent. One of the reasons that may account for this inconsistency is the lack of consideration of temporal dynamics. To address this limitation, here we studied the dynamic modular organization on resting-state functional magnetic resonance imaging across different stages of Alzheimer's disease using a novel multilayer brain network approach. Participants from preclinical and clinical Alzheimer's disease stages were included. Temporal multilayer networks were used to assess time-varying modular organization. Logistic regression models were employed for disease stage discrimination, and partial least squares analyses examined associations between dynamic measures with cognition and pathology. Temporal multilayer functional measures distinguished all groups, particularly preclinical stages, overcoming the discriminatory power of risk factors such as age, sex, and APOE epsilon 4 carriership. Dynamic multilayer functional measures exhibited strong associations with cognition as well as amyloid and tau pathology. Dynamic multilayer functional connectivity shows promise as a functional imaging biomarker for both early- and late-stage Alzheimer's disease diagnosis.
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| 5. |
- Canal-Garcia, A., et al.
(författare)
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Multiplex Connectome Changes across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data
- 2022
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 32:16, s. 3501-3515
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Tidskriftsartikel (refereegranskat)abstract
- The organization of the Alzheimer's disease (AD) connectome has been studied using graph theory using single neuroimaging modalities such as positron emission tomography (PET) or structural magnetic resonance imaging (MRI). Although these modalities measure distinct pathological processes that occur in different stages in AD, there is evidence that they are not independent from each other. Therefore, to capture their interaction, in this study we integrated amyloid PET and gray matter MRI data into a multiplex connectome and assessed the changes across different AD stages. We included 135 cognitively normal (CN) individuals without amyloid-beta pathology (A beta-) in addition to 67 CN, 179 patients with mild cognitive impairment (MCI) and 132 patients with AD dementia who all had A beta pathology (A beta+) from the Alzheimer's Disease Neuroimaging Initiative. We found widespread changes in the overlapping connectivity strength and the overlapping connections across A beta-positive groups. Moreover, there was a reorganization of the multiplex communities in MCI A beta + patients and changes in multiplex brain hubs in both MCI A beta + and AD A beta + groups. These findings offer a new insight into the interplay between amyloid-beta pathology and brain atrophy over the course of AD that moves beyond traditional graph theory analyses based on single brain networks.
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| 6. |
- Chen, Meng, et al.
(författare)
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Neural Progenitor Cells in Cerebral Cortex of Epilepsy Patients do not Originate from Astrocytes Expressing GLAST.
- 2017
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Ingår i: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 27:12, s. 5672-5682
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis in human brain is known to occur in the hippocampus, the subventricular zone, and the striatum. Neural progenitor cells (NPCs) were reported in the cortex of epilepsy patients; however, their identity is not known. Since astrocytes were proposed as the source of neural progenitors in both healthy and diseased brain, we tested the hypothesis that NPCs in the epileptic cortex originate from reactive, alternatively, de-differentiated astrocytes that express glutamate aspartate transporter (GLAST). We assessed the capacity to form neurospheres and the differentiation potential of cells dissociated from fresh cortical tissue from patients who underwent surgical treatment for pharmacologically intractable epilepsy. Neurospheres were generated from 57% of cases (8/14). Upon differentiation, the neurosphere cells gave rise to neurons, oligodendrocytes, and astrocytes. Sorting of dissociated cells showed that only cells negative for GLAST formed neurospheres. In conclusion, we show that cells with neural stem cell properties are present in brain cortex of epilepsy patients, and that these cells are not GLAST-positive astrocytes.
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| 7. |
- Deluca, Vincent, et al.
(författare)
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Mapping individual aspects of bilingual experience to adaptations in brain structure
- 2024
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Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199. ; 34:2
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Tidskriftsartikel (refereegranskat)abstract
- Individual differences in using multiple languages are thought to differentially affect brain structure and function. The present study assessed the neuroanatomical predictions of an emerging theory, the Unifying the Bilingual Experience Trajectories framework, which provides the most comprehensive set of predictions of how individual differences in bilingual experiences lead to specific neural and cognitive adaptations. A total of 140 young adults with variable language experiences were scanned using magnetic resonance imaging and completed demographic questionnaires. Brain structure measures implicated in predictions of the Unifying the Bilingual Experience Trajectories model were extracted and regressed against the model's experiential factors. Consistent with the model's predictions, greater intensity and diversity of bilingual language use resulted in changes in gray matter volume in cortical regions involved in executive control (including inferior frontal gyrus, middle temporal gyrus, angular gyrus, and medial frontal gyrus), indicating adaptations toward handling increased executive control demands. Conversely, duration of bilingual engagement resulted in changes within white matter microstructure (bilateral superior longitudinal fasciculus) and increases in subcortical gray matter (left caudate), indicative of adaptations toward increased efficiency of control. Overall, this research enhances our understanding of how bilingual experiences influence brain structure and provides the first direct empirical evidence for the predictions made by the Unifying the Bilingual Experience Trajectories framework.
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| 8. |
- Fjell, Anders M, et al.
(författare)
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Brain Atrophy in Healthy Aging Is Related to CSF Levels of A{beta}1-42.
- 2010
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Ingår i: Cerebral cortex. - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 20:9, s. 2069-2079
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Tidskriftsartikel (refereegranskat)abstract
- Reduced levels of beta-amyloid(1-42) (Abeta1-42) and increased levels of tau proteins in the cerebrospinal fluid (CSF) are found in Alzheimer's disease (AD), likely reflecting Abeta deposition in plaques and neuronal and axonal damage. It is not known whether these biomarkers are associated with brain atrophy also in healthy aging. We tested the relationship between CSF levels of Abeta1-42 and tau (total tau and tau phosphorylated at threonine 181) proteins and 1-year brain atrophy in 71 cognitively normal elderly individuals. Results showed that under a certain threshold value, levels of Abeta1-42 correlated highly with 1-year change in a wide range of brain areas. The strongest relationships were not found in the regions most vulnerable early in AD. Above the threshold level, Abeta1-42 was not related to brain changes, but significant volume reductions as well as ventricular expansion were still seen. It is concluded that Abeta1-42 correlates with brain atrophy and ventricular expansion in a subgroup of cognitively normal elderly individuals but that reductions independent of CSF levels of Abeta1-42 is common. Further research and follow-up examinations over several years are needed to test whether degenerative pathology will eventually develop in the group of cognitively normal elderly individuals with low levels of Abeta1-42.
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| 9. |
- Fjell, Anders Martin, et al.
(författare)
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Neuroinflammation and Tau Interact with Amyloid in Predicting Sleep Problems in Aging Independently of Atrophy.
- 2018
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Ingår i: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 28:8, s. 2775-2785
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Tidskriftsartikel (refereegranskat)abstract
- Sleep problems relate to brain changes in aging and disease, but the mechanisms are unknown. Studies suggest a relationship between β-amyloid (Aβ) accumulation and sleep, which is likely augmented by interactions with multiple variables. Here, we tested how different cerebrospinal fluid (CSF) biomarkers for brain pathophysiology, brain atrophy, memory function, and depressive symptoms predicted self-reported sleep patterns in 91 cognitively healthy older adults over a 3-year period. The results showed that CSF levels of total- and phosphorylated (P) tau, and YKL-40-a marker of neuroinflammation/astroglial activation-predicted poor sleep in Aβ positive older adults. Interestingly, although brain atrophy was strongly predictive of poor sleep, the relationships between CSF biomarkers and sleep were completely independent of atrophy. A joint analysis showed that unique variance in sleep was explained by P-tau and the P-tau × Aβ interaction, memory function, depressive symptoms, and brain atrophy. The results demonstrate that sleep relates to a range of different pathophysiological processes, underscoring the importance of understanding its impact on neurocognitive changes in aging and people with increased risk of Alzheimer's disease.
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| 10. |
- Fjell, A. M., et al.
(författare)
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Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:4, s. 2144-2156
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Tidskriftsartikel (refereegranskat)abstract
- Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker beta-amyloid (AD) Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homerla, a neural protein coded by the HOMER1 gene, which has also been implicated in brain A beta accumulation. Here, we tested whether the relationship between cortical A beta accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, A beta correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-A beta relationship followed closely the A beta accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and A beta accumulation may involve Homer1 activity in the cortical regions, where harbor A beta deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.
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