PICALM Alzheimer's risk allele causes aberrant lipid droplets in microglia.

ABSTRACT: Despite genome-wide association studies (GWAS) of late-onset Alzheimer's disease (LOAD) having identified many genetic risk loci^1-3, the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent stem (iPS)-cell-derived neurons, astrocytes and microglia, and linked a PICALM LOAD-risk allele to a microglial-specific role of PICALM in lipid droplet (LD) accumulation. Allele-specific open-chromatin mapping revealed functional risk variants for 26 LOAD-risk loci, mostly specific to micro

SUBMITTER: Kozlova A 

PROVIDER: S-EPMC12571902 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature