{"doi":"10.1038/s41593-023-01334-3","title":"Single-nucleus multiregion transcriptomic analysis of brain vasculature in Alzheimer’s disease","abstract":"Cerebrovascular dysregulation is a hallmark of Alzheimer's disease (AD), but the changes that occur in specific cell types have not been fully characterized. Here, we profile single-nucleus transcriptomes in the human cerebrovasculature in six brain regions from 220 individuals with AD and 208 age-matched controls. We annotate 22,514 cerebrovascular cells, including 11 subtypes of endothelial, pericyte, smooth muscle, perivascular fibroblast and ependymal cells. We identify 2,676 differentially expressed genes in AD, including downregulation of PDGFRB in pericytes, and of ABCB1 and ATP10A in endothelial cells, and validate the downregulation of SLC6A1 and upregulation of APOD, INSR and COL4A1 in postmortem AD brain tissues. We detect vasculature, glial and neuronal coexpressed gene modules, suggesting coordinated neurovascular unit dysregulation in AD. Integration with AD genetics reveals 125 AD differentially expressed genes directly linked to AD-associated genetic variants. Lastly, we show that APOE4 genotype-associated differences are significantly enriched among AD-associated genes in capillary and venule endothelial cells, as well as subsets of pericytes and fibroblasts.","journal":"Nature Neuroscience","year":2023,"id":2594,"datarank":2.466716924924195,"base_score":4.897839799950911,"endowment":4.897839799950911,"self_citation_contribution":0.7346759699926367,"citation_network_contribution":1.7320409549315583,"self_endowment_contribution":0.7346759699926367,"citer_contribution":1.7320409549315583,"corpus_percentile":66.1513425549227,"corpus_rank":417,"citation_count":148,"citer_count":129,"citers_with_citation_signal":93,"citers_with_endowment":93,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5892,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-06-01","fair_score":33.8333,"fair_percentile":16.13896218117854,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11610,"name":"Leyla Anne Akay","orcid":"0000-0002-5944-2466","position":1,"is_corresponding":false},{"id":11595,"name":"Mitchell H. 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Bennett","orcid":"0000-0003-3689-554X","position":10,"is_corresponding":false},{"id":11618,"name":"Li-Huei Tsai","orcid":"0000-0003-1262-0592","position":11,"is_corresponding":false},{"id":14693,"name":"Sharon L. R. Kardia","orcid":"0000-0002-9853-3379","position":12,"is_corresponding":false},{"id":11597,"name":"Na Sun","orcid":"0000-0002-9540-8206","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"37264161","pmcid":"PMC10464935","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":69.0,"fair_a":48.0,"fair_i":5.0,"fair_r":13.3333,"fair_zscore":-1.0292,"fair_rationale":{"fair_score":33.83,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":69.0,"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":0.25,"signal":null,"rationale":"The text provides high-level descriptions but no mention of machine-readable metadata, persistent identifiers, or structured metadata schemas."}]},"A":{"name":"Accessible","score":48.0,"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 data/code access protocol","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"No data or code access protocol, repository link, or any access instructions are mentioned in the provided text."}]},"I":{"name":"Interoperable","score":5.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"Standard biological terms (e.g., gene symbols) are used, but there is no mention of standard data formats, controlled vocabularies, or formal identifiers for data or variables."}]},"R":{"name":"Reusable","score":13.33,"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":0.0,"signal":null,"rationale":"No data-availability statement, license, or reproducibility information (e.g., software version, analysis code) is provided in the extracted text."}]}},"suggestions":["Include a structured data-availability statement with a repository link, persistent identifiers (e.g., GEO accession), and a clear access protocol.","Provide code and analysis pipelines in a version-controlled public repository with a license (e.g., MIT, CC-BY).","Describe metadata using standard schemas (e.g., DCAT, schema.org) and include controlled vocabularies (e.g., Cell Ontology, GO) in supplementary materials."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"abstract_only"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"abstract_only","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:38:06.315503Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}