{"doi":"10.1002/alz.12851","title":"Blood levels of MCP‐1 modulate the genetic risks of Alzheimer's disease mediated by HLA‐DRB1 and APOE for Alzheimer's disease","abstract":"INTRODUCTION: C-Reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are both implicated in the peripheral proinflammatory cascade and blood-brain barrier (BBB) disruption. Since the blood CRP level increases Alzheimer's disease (AD) risk depending on the apolipoprotein E (APOE) genotype, we hypothesized that the blood MCP-1 level exerts different effects on the AD risk depending on the genotypes. METHODS: Using multiple regression analyses, data from the Framingham Heart Study (n = 2884) and Alzheimer's Disease Neuroimaging Initiative study (n = 231) were analyzed. RESULTS: An elevated blood MCP-1 level was associated with AD risk in major histocompatibility complex, Class II, DR beta 1 (HLA-DRB1) rs9271192-AC/CC (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.50-6.28, p = 0.002) and in APOE ε4 carriers (HR = 3.22, 95% CI = 1.59-6.53, p = 0.001). In contrast, among HLA-DRB1 rs9271192-AA and APOE ε4 noncarriers, blood MCP-1 levels were not associated with these phenotypes. DISCUSSION: Since HLA-DRB1 and APOE are expressed in the BBB, blood MCP-1 released in the peripheral inflammatory cascade may function as a mediator of the effects of HLA-DRB1 rs9271192-AC/CC and APOE ε4 genotypes on AD pathogenesis in the brain via the BBB pathways.","journal":"Alzheimer s & Dementia","year":2022,"id":262622,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271281,"name":"Thor D. Stein","orcid":"0000-0001-6954-4477","position":1,"is_corresponding":false},{"id":719599,"name":"Yixuan Wang","orcid":"0000-0002-2867-4512","position":2,"is_corresponding":false},{"id":471169,"name":"Ting Fang Alvin Ang","orcid":"0000-0003-4687-2552","position":3,"is_corresponding":false},{"id":857481,"name":"Qiushan Tao","orcid":"0000-0002-1852-3681","position":4,"is_corresponding":false},{"id":24988,"name":"Kathryn L. Lunetta","orcid":"0000-0002-9268-810X","position":5,"is_corresponding":false},{"id":263000,"name":"Joseph M. Massaro","orcid":"0000-0002-2682-4812","position":6,"is_corresponding":false},{"id":291160,"name":"Samia C. Akhter‐Khan","orcid":"0000-0002-5037-3636","position":7,"is_corresponding":false},{"id":261843,"name":"Jesse Mez","orcid":"0000-0003-1438-5442","position":8,"is_corresponding":false},{"id":227481,"name":"Rhoda Au","orcid":"0000-0001-7742-4491","position":9,"is_corresponding":false},{"id":27609,"name":"Lindsay A. Farrer","orcid":"0000-0001-5533-4225","position":10,"is_corresponding":false},{"id":561977,"name":"Xiaoling Zhang","orcid":"0000-0003-0868-1923","position":11,"is_corresponding":false},{"id":493568,"name":"Wei Qiao Qiu","orcid":"0000-0002-2082-2410","position":12,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":13,"is_corresponding":false},{"id":900492,"name":"Jinghan Huang","orcid":"0000-0003-0628-6022","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:26:25.074177Z","pmid":"36396603","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":[]}