Hypothesis-based investigation of known AD risk variants reveals the genetic underpinnings of neuropathological lesions observed in Alzheimer's-type dementia.

ABSTRACT: Alzheimer's disease (AD) is the leading cause of dementia worldwide. Besides neurofibrillary tangles and amyloid beta (Aβ) plaques, a wide range of co-morbid neuropathological features can be observed in AD brains. Since AD has a very strong genetic background and displays a wide phenotypic heterogeneity, this study aims at investigating the genetic underpinnings of co-morbid and hallmark neuropathological lesions. This was realized by obtaining the genotypes for 75 AD risk variants from low-coverage whole-genome sequencing data for 325 individuals from the Leuven Brain Collection. Association testing with deeply characterized neuropathological lesions revealed a strong and likely direct effect of rs117618017, a SNP in exon 1 of APH1B, with tau-related pathology. Second, a relation between

SUBMITTER: Laureyssen C 

PROVIDER: S-EPMC11489263 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature