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- Palpatzis, Eleni, et al.
(författare)
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Lifetime Stressful Events Associated with Alzheimer's Pathologies, Neuroinflammation and Brain Structure in a Risk Enriched Cohort
- 2024
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Ingår i: ANNALS OF NEUROLOGY. - 0364-5134 .- 1531-8249. ; 95:6, s. 1058-1068
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.MethodsThis cross-sectional cohort study included 1,290 CU participants (aged 48-77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)-tau181 and A beta 1-42/1-40 ratio, (2) interleukin 6 (IL-6), and (3) GM volumes voxel-wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.ResultsWithin the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p-tau181 and IL-6. Participants with history of psychiatric disease and men, showed lower A beta 1-42/1-40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.InterpretationWe did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024
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| 2. |
- Warmenhoven, Noelle, et al.
(författare)
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CSF glial biomarkers are associated with cognition in individuals at risk of Alzheimer's disease
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We examined whether baseline glial markers soluble triggering receptor expressed on myeloid cell 2 (sTREM2), chitinase 3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF), and plasma GFAP are associated with cognitive change in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD). METHODS: A total of 353 CU (mean age 60.9 years) participants were included (mean follow-up time 3.28 years). Linear regression models with cognition as outcome were used. We also tested whether amyloid beta (A beta) status modified these associations. RESULTS: Higher baseline CSF sTREM2 was associated with a positive global cognition (Preclinical Alzheimer's Cognitive Composite) rate of change, and better memory and executive outcomes, independently of AD pathology. Higher baseline plasma GFAP was associated with a decline on attention rate of change. Stratified analyses by A beta status showed that CSF sTREM2 and YKL-40 were positively associated with executive functioning in amyloid negative (A beta-) individuals. DISCUSSION: Our results suggest that a TREM2-mediated microglial response may be associated with better longitudinal cognitive performance.
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