Journal Article

FZJ-2019-04457

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Pathway-Specific Genetic Risk for Alzheimer's Disease Differentiates Regional Patterns of Cortical Atrophy in Older Adults

Caspers, S. (Corresponding author)FZJ* ; Röckner, M. E. ; Jockwitz, C.FZJ* ; Bittner, N.FZJ* ; Teumer, A. ; Herms, S. ; Hoffmann, P. ; Nöthen, M. M. ; Moebus, S. ; Amunts, K.FZJ* ; Cichon, S. (Corresponding author)FZJ* ; Mühleisen, T. W.FZJ*

2020
Oxford Univ. Press Oxford

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Please use a persistent id in citations: http://hdl.handle.net/2128/24590  doi:10.1093/cercor/bhz127

Abstract: Brain aging is highly variable and represents a challenge to delimit aging from disease processes. Moreover, genetic factors may influence both aging and disease. Here we focused on this issue and investigated effects of multiple genetic loci previously identified to be associated with late-onset Alzheimer's disease (AD) on brain structure of older adults from a population sample. We calculated a genetic risk score (GRS) using genome-wide significant single-nucleotide polymorphisms from genome-wide association studies of AD and tested its effect on cortical thickness (CT). We observed a common pattern of cortical thinning (right inferior frontal, left posterior temporal, medial occipital cortex). To identify CT changes by specific biological processes, we subdivided the GRS effect according to AD-associated pathways and performed follow-up analyses. The common pattern from the main analysis was further differentiated by pathway-specific effects yielding a more bilateral pattern. Further findings were located in the superior parietal and mid/anterior cingulate regions representing 2 unique pathway-specific patterns. All patterns, except the superior parietal pattern, were influenced by apolipoprotein E. Our step-wise approach revealed atrophy patterns that partially resembled imaging findings in early stages of AD. Our study provides evidence that genetic burden for AD contributes to structural brain variability in normal aging.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)

Research Program(s):

1. 571 - Connectivity and Activity (POF3-571) (POF3-571)
2. HBP SGA2 - Human Brain Project Specific Grant Agreement 2 (785907) (785907)

Appears in the scientific report 2020

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