TY  - JOUR
AU  - Caspers, Svenja
AU  - Röckner, Melanie E
AU  - Jockwitz, Christiane
AU  - Bittner, Nora
AU  - Teumer, Alexander
AU  - Herms, Stefan
AU  - Hoffmann, Per
AU  - Nöthen, Markus M
AU  - Moebus, Susanne
AU  - Amunts, Katrin
AU  - Cichon, Sven
AU  - Mühleisen, Thomas W
TI  - Pathway-Specific Genetic Risk for Alzheimer's Disease Differentiates Regional Patterns of Cortical Atrophy in Older Adults
JO  - Cerebral cortex
VL  - 30
IS  - 2
SN  - 1460-2199
CY  - Oxford
PB  - Oxford Univ. Press
M1  - FZJ-2019-04457
SP  - 801-811
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:31402375
UR  - <Go to ISI:>//WOS:000530440700029
DO  - DOI:10.1093/cercor/bhz127
UR  - https://juser.fz-juelich.de/record/864800
ER  -