{"doi":"10.1002/alz.13387","title":"Distinct transcriptomic responses to Aβ plaques, neurofibrillary tangles, and <i>APOE</i> in Alzheimer's disease","abstract":"INTRODUCTION: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear. METHODS: We performed laser capture microdissection of amyloid beta (Aβ) plaques, the 50 μm halo around them, tangles with the 50 μm halo around them, and areas distant (> 50 μm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing. RESULTS: Aβ plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes. Aβ plaques had more differentially expressed genes than tangles. We identified a gradient Aβ plaque > peri-plaque > tangle > distant for these changes. AD APOE ε4 homozygotes had greater changes than APOE ε3 across locations, especially within Aβ plaques. DISCUSSION: Transcriptomic changes in AD consist primarily of neuroinflammation and neuronal dysfunction, are spatially associated mainly with Aβ plaques, and are exacerbated by the APOE ε4 allele.","journal":"Alzheimer s & Dementia","year":2023,"id":322226,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9298,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":985481,"name":"Zhaozhi Li","orcid":"0000-0001-5957-4509","position":1,"is_corresponding":false},{"id":985483,"name":"Astrid Wachter","orcid":"0009-0001-3977-7832","position":2,"is_corresponding":false},{"id":1036429,"name":"Srinija Alla","orcid":null,"position":3,"is_corresponding":false},{"id":985484,"name":"Ayush Noori","orcid":"0000-0003-1420-1236","position":4,"is_corresponding":false},{"id":986037,"name":"Aicha Abdourahman","orcid":null,"position":5,"is_corresponding":false},{"id":985486,"name":"Joseph A. Tamm","orcid":"0000-0002-7977-2809","position":6,"is_corresponding":false},{"id":288924,"name":"Maya E. Woodbury","orcid":"0000-0003-0613-0220","position":7,"is_corresponding":false},{"id":985487,"name":"Robert V. Talanian","orcid":"0000-0002-6221-4923","position":8,"is_corresponding":false},{"id":549961,"name":"Knut Biber","orcid":"0000-0002-8815-1705","position":9,"is_corresponding":false},{"id":985488,"name":"Eric Karran","orcid":"0000-0002-6782-5213","position":10,"is_corresponding":false},{"id":19610,"name":"Bradley T. Hyman","orcid":"0000-0002-7959-9401","position":11,"is_corresponding":false},{"id":228739,"name":"Alberto Serrano‐Pozo","orcid":"0000-0003-0899-7530","position":12,"is_corresponding":false},{"id":45250,"name":"Sudeshna Das","orcid":"0000-0002-9486-6811","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T01:07:42.497873Z","pmid":"37461318","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":[]}