{"doi":"10.1038/s41586-024-07606-7","title":"Single-cell multiregion dissection of Alzheimer’s disease","abstract":"Alzheimer's disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood<sup>1-3</sup>. Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer's disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer's disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer's disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer's disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer's disease pathology.","journal":"Nature","year":2024,"id":9613,"datarank":4.202176466695583,"base_score":5.337538079701318,"endowment":5.337538079701318,"self_citation_contribution":0.8006307119551977,"citation_network_contribution":3.4015457547403853,"self_endowment_contribution":0.8006307119551977,"citer_contribution":3.4015457547403853,"corpus_percentile":70.05695687550855,"corpus_rank":369,"citation_count":256,"citer_count":189,"citers_with_citation_signal":139,"citers_with_endowment":139,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8701,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-07-24","fair_score":39.375,"fair_percentile":20.030782761653473,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":4960,"name":"Carles B. Adsera","orcid":"0000-0001-9212-856X","position":1,"is_corresponding":false},{"id":11610,"name":"Leyla Anne Akay","orcid":"0000-0002-5944-2466","position":2,"is_corresponding":false},{"id":80329,"name":"Ziting Xia","orcid":"0009-0003-6666-7430","position":3,"is_corresponding":false},{"id":1204,"name":"José Dávila-Velderrain","orcid":"0000-0003-0271-6267","position":4,"is_corresponding":false},{"id":24161,"name":"Ayesha P. Ng","orcid":"0000-0001-8283-4436","position":5,"is_corresponding":false},{"id":24160,"name":"Xueqiao Jiang","orcid":"0000-0001-8073-1636","position":6,"is_corresponding":false},{"id":34021,"name":"Ghada Abdelhady","orcid":"0000-0001-9375-0617","position":7,"is_corresponding":false},{"id":24159,"name":"Kyriaki Galani","orcid":null,"position":8,"is_corresponding":false},{"id":5481,"name":"Julio Mantero","orcid":"0000-0003-4694-9708","position":9,"is_corresponding":false},{"id":80330,"name":"Neil Band","orcid":null,"position":10,"is_corresponding":false},{"id":39697,"name":"Benjamin T. James","orcid":"0000-0002-6228-055X","position":11,"is_corresponding":false},{"id":34020,"name":"Sudhagar Babu","orcid":"0000-0001-6012-8936","position":12,"is_corresponding":false},{"id":11605,"name":"Fabiola Galiana-Melendez","orcid":"0009-0006-8926-496X","position":13,"is_corresponding":false},{"id":80331,"name":"Kate Louderback","orcid":null,"position":14,"is_corresponding":false},{"id":24853,"name":"Dmitry Prokopenko","orcid":"0000-0002-1844-5652","position":15,"is_corresponding":false},{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":16,"is_corresponding":false},{"id":778,"name":"David A. Bennett","orcid":"0000-0003-3689-554X","position":17,"is_corresponding":false},{"id":11618,"name":"Li-Huei Tsai","orcid":"0000-0003-1262-0592","position":18,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":19,"is_corresponding":false},{"id":17177,"name":"Hansruedi Mathys","orcid":"0000-0003-0186-2115","position":0,"is_corresponding":true}],"reference_count":121,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"39048816","pmcid":"PMC11338834","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"hybrid","license":"cc-by","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":65.0,"fair_a":42.5,"fair_i":25.0,"fair_r":25.0,"fair_zscore":-0.5279,"fair_rationale":{"fair_score":39.38,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":65.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.5,"signal":null,"rationale":"The paper mentions an online resource (http://compbio.mit.edu/ad_multiregion) and provides details on snRNA-seq data processing, but lacks explicit statements about machine-readable metadata files or structured metadata descriptors."}]},"A":{"name":"Accessible","score":42.5,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear 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cell types from Allen Brain Atlas), but does not explicitly state use of community-standard vocabularies or persistent identifiers for cell types or genes beyond gene symbols."}]},"R":{"name":"Reusable","score":25.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.333,"signal":null,"rationale":"The paper provides a Creative Commons license (CC BY 4.0) and a website for exploration, but no formal data-availability statement, no reference to a public repository with assigned identifiers, and limited details on computational reproducibility (e.g., no explicit container or workflow specification)."}]}},"suggestions":["Deposit raw and processed snRNA-seq data in a public repository (e.g., GEO, EGA) with accession numbers to improve accessibility and reusability.","Provide a formal data-availability statement clearly stating how to access all data and code.","Include machine-readable metadata (e.g., ISA-Tab, DataCite XML) describing samples, variables, and provenance.","Use community-standard vocabularies (e.g., Cell Ontology, UBERON) for cell types and brain regions in supplementary tables.","Provide code and analysis pipelines in a public repository (e.g., GitHub) with versioned releases and a software 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