{"doi":"10.1002/alz.14142","title":"Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration","abstract":"INTRODUCTION: Plasma proteomic analyses of unique brain atrophy patterns may illuminate peripheral drivers of neurodegeneration and identify novel biomarkers for predicting clinically relevant outcomes. METHODS: We identified proteomic signatures associated with machine learning-derived aging- and Alzheimer's disease (AD) -related brain atrophy patterns in the Baltimore Longitudinal Study of Aging (n = 815). Using data from five cohorts, we examined whether candidate proteins were associated with AD endophenotypes and long-term dementia risk. RESULTS: Plasma proteins associated with distinct patterns of age- and AD-related atrophy were also associated with plasma/cerebrospinal fluid (CSF) AD biomarkers, cognition, AD risk, as well as mid-life (20-year) and late-life (8-year) dementia risk. EFEMP1 and CXCL12 showed the most consistent associations across cohorts and were mechanistically implicated as determinants of brain structure using genetic methods, including Mendelian randomization. DISCUSSION: Our findings reveal plasma proteomic signatures of unique aging- and AD-related brain atrophy patterns and implicate EFEMP1 and CXCL12 as important molecular drivers of neurodegeneration. HIGHLIGHTS: Plasma proteomic signatures are associated with unique patterns of brain atrophy. Brain atrophy-related proteins predict clinically relevant outcomes across cohorts. Genetic variation underlying plasma EFEMP1 and CXCL12 influences brain structure. EFEMP1 and CXCL12 may be important molecular drivers of neurodegeneration.","journal":"Alzheimer s & Dementia","year":2024,"id":426121,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8812,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":501328,"name":"Zhijian Yang","orcid":"0000-0002-7863-827X","position":1,"is_corresponding":false},{"id":992346,"name":"Yuhan Cui","orcid":"0000-0002-0017-0056","position":2,"is_corresponding":false},{"id":363726,"name":"Heather E. Dark","orcid":"0000-0001-7194-3637","position":3,"is_corresponding":false},{"id":34917,"name":"Junhao Wen","orcid":"0000-0003-2077-3070","position":4,"is_corresponding":false},{"id":34929,"name":"Guray Erus","orcid":"0000-0001-6633-4861","position":5,"is_corresponding":false},{"id":254761,"name":"Timothy J. Hohman","orcid":"0000-0002-3377-7014","position":6,"is_corresponding":false},{"id":624479,"name":"Jingsha Chen","orcid":null,"position":7,"is_corresponding":false},{"id":895951,"name":"Alexandria Lewis","orcid":"0000-0002-3812-8080","position":8,"is_corresponding":false},{"id":27596,"name":"Abhay Moghekar","orcid":"0000-0001-9464-1551","position":9,"is_corresponding":false},{"id":23021,"name":"Josef Coresh","orcid":"0000-0002-4598-0669","position":10,"is_corresponding":false},{"id":230044,"name":"Susan M. Resnick","orcid":"0000-0003-1115-7145","position":11,"is_corresponding":false},{"id":34918,"name":"Christos Davatzikos","orcid":"0000-0002-1025-8561","position":12,"is_corresponding":false},{"id":34922,"name":"Keenan A. Walker","orcid":"0000-0002-5989-9853","position":13,"is_corresponding":false},{"id":34928,"name":"Michael R. Duggan","orcid":"0000-0002-1029-4423","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T01:58:37.924718Z","pmid":"39129354","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":[]}