{"doi":"10.1002/alz.70381","title":"Plasma NfL and GFAP for predicting VCI and related brain changes in community and clinical cohorts","abstract":"INTRODUCTION: We investigated the usefulness of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) for capturing vascular cognitive impairment (VCI) in the context of amyloidosis. METHODS: Using two independent cohorts (n = 1810), we assessed the relationship of plasma NfL and GFAP with (1) vascular brain indices; (2) diagnostic states using the following definitions: vascular versus not (white matter hyperintensity/total intracranial volume ≥ 1.3%), and cognitively impaired (CI) versus cognitively unimpaired (CU) using Clinical Dementia Rating ([CDR] scale ≥ 0.5); and (3) their upstream predictors using structural equation models (SEMs). RESULTS: Plasma NfL and GFAP were associated with vascular brain damage and differed across states (VCI > vascular CU > non-vascular CI > non-vascular CU). In a population-based sample, these biomarkers distinguished vascular CU and VCI from non-vascular CU groups with greater separation in amyloid negative participants. Pathway analyses showed NfL was primarily influenced by systemic/brain vascular health, whereas amyloid contributed to GFAP variability. DISCUSSION: Plasma biomarkers, particularly NfL, capture vascular brain changes and show promise for VCI identification. HIGHLIGHTS: Plasma NfL and glial fibrillary acidic protein (GFAP) were associated with vascular brain indices. Plasma biomarkers differed across diagnostic states (VCI > vascular CU > non-vascular CI > non-vascular CU). Plasma markers discriminated vascular from non-vascular states with greater separation in Aβ- participants. NfL was linked to vascular health, while amyloid influenced GFAP variability in the population-based sample. Future longitudinal frameworks should consider systemic inflammation markers along with these plasma markers to better understand VCID-related brain changes and cognitive decline.","journal":"Alzheimer s & Dementia","year":2025,"id":511319,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9106,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":253918,"name":"Jonathan Graff‐Radford","orcid":"0000-0003-2770-0691","position":1,"is_corresponding":false},{"id":846780,"name":"Ekaterina I. Hofrenning","orcid":"0000-0003-2266-6746","position":2,"is_corresponding":false},{"id":567109,"name":"Angela J. Fought","orcid":"0000-0002-7486-8596","position":3,"is_corresponding":false},{"id":318670,"name":"Robert I. Reid","orcid":"0000-0003-2391-8650","position":4,"is_corresponding":false},{"id":389157,"name":"Michael G. Kamykowski","orcid":"0000-0002-3108-7618","position":5,"is_corresponding":false},{"id":645161,"name":"Alicia Algeciras‐Schimnich","orcid":"0000-0002-4455-6217","position":6,"is_corresponding":false},{"id":331917,"name":"B. Gwen Windham","orcid":"0000-0001-6240-5044","position":7,"is_corresponding":false},{"id":49955,"name":"David S. Knopman","orcid":"0000-0002-6544-066X","position":8,"is_corresponding":false},{"id":259159,"name":"Val J. Lowe","orcid":"0000-0002-5612-1667","position":9,"is_corresponding":false},{"id":49956,"name":"Clifford R. Jack","orcid":"0000-0001-7916-622X","position":10,"is_corresponding":false},{"id":54269,"name":"Ronald Petersen","orcid":"0009-0006-8296-6416","position":11,"is_corresponding":false},{"id":226058,"name":"Prashanthi Vemuri","orcid":"0000-0003-4286-0589","position":12,"is_corresponding":false},{"id":318669,"name":"Sheelakumari Raghavan","orcid":"0000-0001-8652-7011","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:47:55.918021Z","pmid":"40566826","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":[]}