This hypothesis proposes that APOE contributes to Alzheimer's disease by regulating both beta-amyloid deposition and immune system pathways through distinct cell-type-specific molecular partners.
Type: Mechanistic Proposal
Confidence: Supported
Related Diseases: Alzheimer's disease
Pathway enrichment analysis showed APOE-associated genes in microglia were enriched for complement system, antigen processing/presentation, and prion disease pathways. In astrocytes, pathways included protein processing in ER and antigen processing. Multiple AD GWAS loci (CLU, TREM2) showed co-expression with APOE. CLU, CST3, and ITM2B are involved in regulating beta-amyloid production or fibril formation.
APOE, CLU, CST3, ITM2B, C1Q, TREM2, complement system, beta-amyloid
This hypothesis is supported by multiple lines of evidence from the literature.