Revealing the nervous system requirements of Alzheimer's disease risk genes in <i>Drosophila</i>.

ABSTRACT: Most Alzheimer's disease (AD) susceptibility genes have poorly understood roles in the central nervous system (CNS). To address this gap, we systematically characterized 100 conserved candidate AD risk genes using a cross-species strategy in the fruit fly, Drosophila melanogaster . Genes were prioritized based primarily on human functional genomic evidence. We generated custom, loss-of-function alleles for each of the conserved fly orthologs. Most of the genes (80%) are expressed in the adult brain, including 24 neuron- and 13 glia-specific expression patterns. Overall, we identify 50 candidate AD risk gene homologs with requirements for CNS structure or function, including 18 whose loss of function causes neurodegeneration (e.g., Snx6/SNX32 and ClC-a/CLCN1 ), 35 requi

SUBMITTER: Deger JM 

PROVIDER: S-EPMC12324250 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature