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The evaluation of A\u03b2, tau, and neurodegenerative (A\/T\/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A\/T\/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer\u2019s Disease Neuroimaging Initiative dataset, we show that A\/T\/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of A\u03b2 and tau better predicting early dementia status, and biomarkers of neurodegeneration, especially glucose hypometabolism, better predicting later dementia status. Our results suggest that AD treatments may also need to be disease stage-oriented with A\u03b2 and tau as targets in early AD and glucose metabolism as a target in later AD.<\/jats:p>","DOI":"10.1038\/s42003-020-1079-x","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T10:03:14Z","timestamp":1594029794000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["\u03b2-amyloid and tau drive early Alzheimer\u2019s disease decline while glucose hypometabolism drives late decline"],"prefix":"10.1038","volume":"3","author":[{"given":"Tyler C.","family":"Hammond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangsik","family":"Nho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul K.","family":"Crane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Elahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-7417","authenticated-orcid":false,"given":"David A.","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-6664","authenticated-orcid":false,"given":"Gongbo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille M.","family":"Yanckello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4242-8967","authenticated-orcid":false,"given":"Nathan","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-2219","authenticated-orcid":false,"given":"Ai-Ling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"1079_CR1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.pharep.2014.09.004","volume":"67","author":"A Kumar","year":"2015","unstructured":"Kumar, A., Singh, A. & Ekavali A review on Alzheimer\u2019s disease pathophysiology and its management: an update. 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