APOE genotype shapes lipid droplet composition and dynamics in human astrocytes

ABSTRACT: Lipid droplets are dynamic organelles involved in cellular functions ranging from lipid storage regulation to immune modulation. The proteins that localize to the lipid droplet membrane play a critical role in determining these functions. Recent research has highlighted the involvement of glial lipid droplets in the pathology and progression of late-onset Alzheimer’s disease. APOE, a gene encoding a lipid-binding and transport protein, is a major genetic determinant of Alzheimer’s disease risk, with different variants conferring risk or protection. In this study, we characterized the human astrocytic lipid droplet proteome and found that each APOE variant–risk, benign, and protective–produces a distinct proteomic profile in astrocytes. These variant-specific proteomes influence lipid droplet biology and broader aspects of cellular physiology. Moreover, we discovered that changes in the lipid droplet proteome directly affect the turnover and dynamics of lipid droplets in astrocytes across different APOE genotypes. Together, these findings provide new insights into how APOE variants reshape astrocyte biology and identify lipid droplets as a modifiable aspect of Alzheimer’s disease pathology.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Yue Andy Qi  

LAB HEAD: Ying Hao

PROVIDER: PXD067161 | Pride | 2026-07-01

REPOSITORIES: Pride