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Variables included: CSF phosphorylated tau (p\u2010tau181), hippocampal and whole\u2010brain volume, logical memory (LM), composite Trail Making Test score, and white matter hyperintensity (WMH) volumes. CSF amyloid\u2010negative, apolipoprotein E \u03b54 non\u2010carrier cognitively unimpaired controls (<jats:italic>n\u00a0<\/jats:italic>=\u00a086) were used to calculate <jats:italic>z<\/jats:italic> scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>One subtype (<jats:italic>n\u00a0<\/jats:italic>=\u00a0145) had early LM changes, with later p\u2010tau and WMH changes. A second subtype (<jats:italic>n\u00a0<\/jats:italic>=\u00a088) had early WMH changes, were older, and more hypertensive. A third subtype (<jats:italic>n\u00a0<\/jats:italic>=\u00a0100) had early p\u2010tau changes, and reflected typical Alzheimer's disease. Some amyloid positive (<jats:italic>n\u00a0<\/jats:italic>=\u00a043) individuals were similar to the amyloid\u2010negative group.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>This work identified heterogeneity in individuals who are conventionally considered homogeneous, which is likely driven by co\u2010pathologies including cerebrovascular disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Data\u2010driven modeling identified marker heterogeneity in amyloid\u2010positive individuals.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Heterogeneity reflected Alzheimer's disease\u2010like, vascular\u2010like, and mixed pathology presentations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Some amyloid\u2010positive individuals were more similar to amyloid\u2010negative controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Vascular pathology plays a key role in understanding heterogeneity in those on the amyloid pathway.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14287","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T06:44:33Z","timestamp":1729147473000},"page":"8503-8515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biomarker pathway heterogeneity of amyloid\u2010positive individuals"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-1525","authenticated-orcid":false,"given":"Lloyd","family":"Prosser","sequence":"first","affiliation":[{"name":"Dementia Research Centre Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology Queen Square  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole H.","family":"Sudre","sequence":"additional","affiliation":[{"name":"Dementia Research Centre 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