{"doi":"10.1016/j.celrep.2025.115422","title":"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, transcriptional changes associated with intraneuronal tau in PART and AD were similar, suggesting a possible mechanistic relationship. These findings highlight the power of molecular analysis stratified by pathology and provide insight into common pathways associated with tau pathology in PART and AD.","journal":"Cell Reports","year":2025,"id":511749,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9354,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":347390,"name":"Ryan G. Palaganas","orcid":"0000-0003-1435-8874","position":1,"is_corresponding":false},{"id":780834,"name":"E. Michael Meyer","orcid":null,"position":2,"is_corresponding":false},{"id":577284,"name":"Javier Redding‐Ochoa","orcid":"0000-0002-0677-917X","position":3,"is_corresponding":false},{"id":256963,"name":"Olga Pletnikova","orcid":null,"position":4,"is_corresponding":false},{"id":615680,"name":"Haidan Guo","orcid":"0009-0000-9678-1777","position":5,"is_corresponding":false},{"id":453212,"name":"William R. Bell","orcid":"0000-0001-6326-3885","position":6,"is_corresponding":false},{"id":107084,"name":"Juan C. Troncoso","orcid":"0000-0001-9553-6673","position":7,"is_corresponding":false},{"id":275418,"name":"Richard L. Huganir","orcid":"0000-0001-9783-5183","position":8,"is_corresponding":false},{"id":640288,"name":"Meaghan Morris","orcid":"0000-0001-5340-148X","position":9,"is_corresponding":false},{"id":31860,"name":"Genevieve L. Stein-O’Brien","orcid":"0000-0001-8681-9110","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:48:01.269605Z","pmid":"40085647","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}