{"doi":"10.1016/j.cccb.2022.100131","title":"Platelet-derived growth factor-BB and white matter hyperintensity burden in APOE4 carriers","abstract":"The apolipoprotein-e4 (APOE4) gene increases risk for developing late-onset Alzheimer's disease (AD) and has been linked to increased microvascular dysfunction, including pericyte degeneration and blood-brain barrier breakdown. Platelet-derived growth factor-BB (PDGF-BB) is a glycoprotein involved in blood-brain barrier and pericyte maintenance. Increased PDGF-BB levels have been reported in white matter in AD brain tissue. However, the association between circulating levels of PDGF-BB and cerebral white matter damage in older adults remains unknown. Participants included community-dwelling older adults (age range 55–90 years, M = 73.1 years; SD = 7.5; 61.0% male) from the Alzheimer's Disease Neuroimaging Initiative who underwent venipuncture and blood plasma immunoassay for PDGF-BB, brain MRI scanning with T2-FLAIR for volumetric quantification of white matter hyperintensities (WMH) and APOE4 genotyping (N = 64). Linear regression analyses examined the relationship between plasma PDGF-BB levels and WMH volume, adjusting for age, sex, intracranial volume (ICV) and stratifying by APOE4 status. Greater levels of circulating PDGF-BB were related to greater WMH volume, even after accounting for age, sex, ICV and APOE4 carrier status (p = 0.040). Nineteen (29.2%) were APOE4 carriers. When stratified by APOE4 status, the relationship between PDGF-BB and WMH volume was only significant for APOE4 carriers (p = 0.007), but not non-carriers (p = 0.448), after adjusting for age, sex and ICV. These findings reveal a differential relationship between PDGF-BB and WMH volume for APOE4 carriers versus non-carriers. The APOE4 variant leads to accelerated cerebrovascular injury and cognitive decline. Elevated levels of PDGF-BB in carriers may suggest a role for pericytes and blood-brain barrier dysfunction in white matter damage, vascular cognitive impairment and AD. Additional studies will elucidate the role of PDGF ligands and receptors in these conditions.","journal":"Cerebral Circulation - Cognition and Behavior","year":2022,"id":257262,"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":0.9604,"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":283896,"name":"Daniel A. Nation","orcid":"0000-0002-9123-0658","position":1,"is_corresponding":false},{"id":283895,"name":"Arunima Kapoor","orcid":"0000-0003-4622-8951","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:25:30.183987Z","pmid":"35844252","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":[]}