{"doi":"10.1002/alz.14287","title":"Biomarker pathway heterogeneity of amyloid‐positive individuals","abstract":"INTRODUCTION: In amyloid-positive individuals, disease-related biomarker heterogeneity is understudied. METHODS: We used Subtype and Stage Inference (SuStaIn) to identify data-driven subtypes among cerebrospinal fluid (CSF) amyloid beta (1-42)-positive individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNIGO/2 [n = 376]). Variables included: CSF phosphorylated tau (p-tau181), hippocampal and whole-brain volume, logical memory (LM), composite Trail Making Test score, and white matter hyperintensity (WMH) volumes. CSF amyloid-negative, apolipoprotein E ε4 non-carrier cognitively unimpaired controls (n = 86) were used to calculate z scores. RESULTS: One subtype (n = 145) had early LM changes, with later p-tau and WMH changes. A second subtype (n = 88) had early WMH changes, were older, and more hypertensive. A third subtype (n = 100) had early p-tau changes, and reflected typical Alzheimer's disease. Some amyloid positive (n = 43) individuals were similar to the amyloid-negative group. DISCUSSION: This work identified heterogeneity in individuals who are conventionally considered homogeneous, which is likely driven by co-pathologies including cerebrovascular disease. HIGHLIGHTS: Data-driven modeling identified marker heterogeneity in amyloid-positive individuals. Heterogeneity reflected Alzheimer's disease-like, vascular-like, and mixed pathology presentations. Some amyloid-positive individuals were more similar to amyloid-negative controls. Vascular pathology plays a key role in understanding heterogeneity in those on the amyloid pathway.","journal":"Alzheimer s & Dementia","year":2024,"id":456669,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5038,"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":104580,"name":"Carole H. Sudre","orcid":"0000-0001-5753-428X","position":1,"is_corresponding":false},{"id":318443,"name":"Neil P. Oxtoby","orcid":"0000-0003-0203-3909","position":2,"is_corresponding":false},{"id":318444,"name":"Alexandra L. Young","orcid":"0000-0002-7772-781X","position":3,"is_corresponding":false},{"id":67955,"name":"Ian B. Malone","orcid":"0000-0001-7512-7856","position":4,"is_corresponding":false},{"id":502486,"name":"Emily N. Manning","orcid":"0000-0002-4505-3611","position":5,"is_corresponding":false},{"id":502485,"name":"Hugh Pemberton","orcid":"0000-0001-8419-6423","position":6,"is_corresponding":false},{"id":348758,"name":"Phoebe Walsh","orcid":"0000-0001-6584-3111","position":7,"is_corresponding":false},{"id":242544,"name":"Frederik Barkhof","orcid":"0000-0003-3543-3706","position":8,"is_corresponding":false},{"id":363430,"name":"Geert Jan Biessels","orcid":"0000-0001-6862-2496","position":9,"is_corresponding":false},{"id":320896,"name":"David M. Cash","orcid":"0000-0001-7833-616X","position":10,"is_corresponding":false},{"id":348762,"name":"Josephine Barnes","orcid":"0000-0003-3178-025X","position":11,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":12,"is_corresponding":false},{"id":899966,"name":"Lloyd Prosser","orcid":"0000-0003-0299-1525","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:03:32.516678Z","pmid":"39417393","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":[]}