Cell type-resolved proteomics reveals intra- and intercellular signaling in Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) arises from pathological interactions among diverse brain cell types, but cell-specific proteomic changes remain underexplored. Here, we present deep proteomic profiling of sorted or proximity-labeled brain cells from AD mouse models (5xFAD and App ^NL-G-F ) at multiple ages, quantifying 13,411 proteins in microglia (three subtypes), astrocytes, oligodendrocyte precursor cells, and neurons. We identified 3,028 differentially abundant proteins across these cell types, the majority of which were not detected in bulk proteomic datasets, and constructed cell type-specific networks to define functional modules and hub proteins. Comparison with transcriptomic data revealed that ∼30% of proteomic changes are RNA-independent. Further analyses uncovered cross-cell

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12889647 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature