Genome-wide and gene-specific studies have revealed differential DNA methylation patterns in AD brains and peripheral tissues—such as hypomethylation at APOE and TREM2 loci, hypermethylation of BDNF (brain-derived neurotrophic factor) and SPINT1 (Serine Peptidase Inhibitor, Kunitz Type 1) promoters, and global methylation shifts linked to APOE ε4 status that correlate with disease progression and cognitive decline, suggesting their utility as diagnostic or prognostic biomarkers [76]. Here, APOE is linked to Alzheimer disease.