Bulk and Single-Nucleus Transcriptomics Highlight Intra-Telencephalic and Somatostatin Neurons in Alzheimer's Disease.

ABSTRACT: Cortical neuron loss is a pathological hallmark of late-onset Alzheimer's disease (AD). However, it remains unclear which neuronal subtypes beyond broad excitatory and inhibitory classes are most vulnerable. Here, we analyzed cell subtype proportion differences in AD compared to non-AD controls using 1037 post-mortem brain samples from six neocortical regions. We identified the strongest associations of AD with fewer somatostatin (SST) inhibitory neurons (β = -0.48, p _bonf = 8.98 × 10^-9) and intra-telencephalic (IT) excitatory neurons (β = -0.45, p _bonf = 4.32 × 10^-7). Replication in three AD case-control single-nucleus RNAseq datasets most strongly supported the bulk tissue association of fewer SST neurons in AD. In d

SUBMITTER: Consens ME 

PROVIDER: S-EPMC9231610 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature