Molecular estimation of neurodegeneration pseudotime in older brains.

ABSTRACT: The temporal molecular changes that lead to disease onset and progression in Alzheimer's disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage-or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10^-5), Aβ (CERAD score, P = 1.8 × 10^-5), and cognitive diagnosis (P = 3.5 × 10^-7) of late-onset (LO) AD. Early stage disease pseudotime sa

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC7666177 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature