A familial missense variant in the Alzheimer's Disease gene SORL1 impairs its maturation and endosomal sorting.

ABSTRACT: The SORL1 gene has recently emerged as a strong Alzheimer's Disease (AD) risk gene. Over 500 different variants have been identified in the gene and the contribution of individual variants to AD development and progression is still largely unknown. Here, we describe a family consisting of 2 parents and 5 offspring. Both parents were affected with dementia and one had confirmed AD pathology with an age of onset >75 years. All offspring were affected with AD with ages at onset ranging from 53yrs-74yrs. DNA was available from the parent with confirmed AD and 5 offspring. We identified a coding variant, p.(Arg953Cys), in SORL1 in 5 of 6 individuals affected by AD. Notably, variant carriers had severe AD pathology, and the SORL1 variant segregated with TDP-43 pathology (LAT

SUBMITTER: Fazeli E 

PROVIDER: S-EPMC10349966 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature