APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.

ABSTRACT: APOE4 is the strongest genetic risk factor for Alzheimer's disease^1-3. However, the effects of APOE4 on the human brain are not fully understood, limiting opportunities to develop targeted therapeutics for individuals carrying APOE4 and other risk factors for Alzheimer's disease^4-8. Here, to gain more comprehensive insights into the impact of APOE4 on the human brain, we performed single-cell transcriptomics profiling of post-mortem human brains from APOE4 carriers compared with non-carriers. This revealed that APOE4 is associated with widespread gene expression changes across all cell types of the human brain. Consistent with the biological function of APOE^2-6, APOE4 significantly altered signalling pathways associated with cholesterol homeostasis and tran

SUBMITTER: Blanchard JW 

PROVIDER: S-EPMC9870060 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature