Transcriptional signatures of hippocampal tau pathology in primary age-related tauopathy and Alzheimer's disease.

ABSTRACT: In primary age-related tauopathy (PART) and Alzheimer's disease (AD), tau aggregates share a similar structure and anatomic distribution, which is distinct from tau pathology in other diseases. However, transcriptional similarities between PART and AD and gene expression changes within tau-pathology-bearing neurons are largely unknown. Using GeoMx spatial transcriptomics, mRNA was quantified in hippocampal neurons with and without tau pathology in PART and AD. Synaptic genes were down-regulated in disease overall but up-regulated in tau-pathology-positive neurons. Two transcriptional signatures were associated with intraneuronal tau, both validated in a cortical AD dataset. Genes in the up-regulated signature were enriched in calcium regulation and synaptic function. Notably, transcription

SUBMITTER: Stein-O'Brien GL 

PROVIDER: S-EPMC12019863 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature