{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:19:44Z","timestamp":1792815584878,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-\u03b21-42 (A\u03b242), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis. Methods: We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD. Methods: We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD. Results: In additional to A\u03b2 and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and\/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and na\u00efve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls. Conclusions: Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.<\/jats:p>","DOI":"10.3390\/ijms22052761","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T06:22:32Z","timestamp":1615270952000},"page":"2761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":226,"title":["Machine Learning and Novel Biomarkers for the Diagnosis of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2949-5855","authenticated-orcid":false,"given":"Chun-Hung","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychiatry &amp; Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan"},{"name":"An Nan Hospital, China Medical University, Tainan 709025, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Hsin","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"},{"name":"Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"School of Medicine, Chang Gung University, Taoyuan 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-8174","authenticated-orcid":false,"given":"Hsien-Yuan","family":"Lane","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychiatry &amp; Brain Disease Research Center, China Medical University Hospital, Taichung 40402, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/S1474-4422(16)30356-8","article-title":"Alzheimer\u2019s disease and other dementias: Update on research","volume":"16","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1097\/EDE.0000000000000199","article-title":"Prevalence of Alzheimer disease in US states","volume":"26","author":"Weuve","year":"2015","journal-title":"Epidemiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.4103\/1673-5374.286957","article-title":"Application of modern neuroimaging technology in the diagnosis and study of Alzheimer\u2019s disease","volume":"16","author":"Zeng","year":"2021","journal-title":"Neural Regen. 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