Epigenomic subtypes of late-onset Alzheimer's disease reveal distinct microglial signatures.

ABSTRACT: Growing evidence suggests that clinical, pathological, and genetic heterogeneity in late-onset Alzheimer's disease (LOAD) contributes to variable therapeutic outcomes, potentially explaining many trial failures. Advances in molecular subtyping through proteomic and transcriptomic profiling reveal distinct patient subgroups, highlighting disease complexity beyond amyloid-beta plaques and tau tangles. This underscores the need to expand subtyping across new molecular layers, to identify novel drug targets for different patient subgroups. In this study, we analyzed genome-wide DNA methylation (DNAm) data from three independent postmortem brain cohorts (N = 826) to identify epigenetic subtypes of LOAD. We used unsupervised clustering to define subtype-specific DNAm patterns and validated them

SUBMITTER: Laroche VT 

PROVIDER: S-EPMC12932393 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature