{"doi":"10.1002/dad2.70081","title":"Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression","abstract":"Abstract INTRODUCTION We examined long‐term plasma biomarker trajectories among participants who were cognitively unimpaired and primarily middle aged at baseline and whether trajectories differed by Alzheimer's disease (AD) genetic risk and among those who developed cognitive impairment. METHODS Plasma amyloid beta (Aβ) 42 /Aβ 40 , phosphorylated tau (p‐tau) 181 , neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells, and chitinase 3‐like protein 1 were measured longitudinally in 177 BIOCARD participants ( M baseline age = 57.7 years; M follow‐up = 15.8 years), including 57 who developed cognitive impairment. Measures of AD genetic risk included apolipoprotein E ( APOE ) ε4 and an AD polygenic risk score (AD‐PRS). RESULTS Compared to non‐carriers, APOE ε4 carriers had lower Aβ 42 /Aβ 40 and greater longitudinal increases in p‐tau 181 and GFAP; in contrast, the AD‐PRS (excluding the APOE region) was associated with greater declines in Aβ 42 /Aβ 40 among APOE ε4 non‐carriers. Rates of increase in p‐tau 181 , NfL, and GFAP were greater among those who later developed cognitive impairment. DISCUSSION Monitoring changes in plasma p‐tau 181 , NfL, and GFAP may be particularly informative during preclinical AD. Highlights We examined plasma biomarker changes in cognitively normal individuals over 15.8 years. Apolipoprotein E ( APOE ) ε4 was related to lower amyloid beta (Aβ) 42 /Aβ 40 and greater increases in phosphorylated tau (p‐tau) 181 and glial fibrillary acidic protein (GFAP). In APOE ε4 non‐carriers, higher Alzheimer's disease (AD) polygenic risk score was related to greater Aβ 42 /Aβ 40 declines. P‐tau 181 , NfL, and GFAP increases were greater among those who progressed to mild cognitive impairment. Results highlight the predictive value of plasma biomarkers during preclinical AD.","journal":"Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring","year":2025,"id":522974,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9196,"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":315436,"name":"Anja Soldan","orcid":"0000-0002-6193-0418","position":1,"is_corresponding":false},{"id":336892,"name":"Jiangxia Wang","orcid":"0000-0002-1715-3981","position":2,"is_corresponding":false},{"id":254761,"name":"Timothy J. Hohman","orcid":"0000-0002-3377-7014","position":3,"is_corresponding":false},{"id":261835,"name":"Logan Dumitrescu","orcid":"0000-0002-9782-9944","position":4,"is_corresponding":false},{"id":19614,"name":"Marilyn Albert","orcid":"0000-0002-8167-8985","position":5,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":6,"is_corresponding":false},{"id":668064,"name":"Tobias Bittner","orcid":"0000-0001-9256-0360","position":7,"is_corresponding":false},{"id":27596,"name":"Abhay Moghekar","orcid":"0000-0001-9464-1551","position":8,"is_corresponding":false},{"id":1177460,"name":"The BIOCARD Study Team","orcid":null,"position":9,"is_corresponding":false},{"id":329631,"name":"Corinne Pettigrew","orcid":"0000-0003-4264-275X","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:49:58.707747Z","pmid":"40151521","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":[]}