Unified epigenomic, transcriptomic, proteomic, and metabolomic taxonomy of Alzheimer's disease progression and heterogeneity.

ABSTRACT: Alzheimer's disease (AD) is a heterogeneous disorder with abnormalities in multiple biological domains. In an advanced machine learning analysis of postmortem brain and in vivo blood multi-omics molecular data (N = 1863), we integrated epigenomic, transcriptomic, proteomic, and metabolomic profiles into a multilevel biological AD taxonomy. We obtained a personalized multilevel molecular index of AD dementia progression that predicts severity of neuropathologies, and identified three robust molecular-based subtypes that explain much of the pathologic and clinical heterogeneity of AD. These subtypes present distinct patterns of alteration in DNA methylation, RNA, proteins, and metabolites, identifiable in the brain and subsequently in blood. In addition, the genetic variations that pr

SUBMITTER: Iturria-Medina Y 

PROVIDER: S-EPMC9674284 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature