Early Alzheimer's disease pathology in human cortex is associated with a transient phase of distinct cell states.

ABSTRACT: Cellular perturbations underlying Alzheimer's disease are primarily studied in human postmortem samples and model organisms. Here we generated a single-nucleus atlas from a rare cohort of cortical biopsies from living individuals with varying degrees of Alzheimer's disease pathology. We next performed a systematic cross-disease and cross-species integrative analysis to identify a set of cell states that are specific to early AD pathology. These changes-which we refer to as the Early Cortical Amyloid Response-were prominent in neurons, wherein we identified a transient state of hyperactivity preceding loss of excitatory neurons, which correlated with the selective loss of layer 1 inhibitory neurons. Microglia overexpressing neuroinflammatory-related processes also expanded as AD pathologica

SUBMITTER: Gazestani V 

PROVIDER: S-EPMC10274680 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature