{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:05:08Z","timestamp":1790697908594,"version":"4.1.0"},"reference-count":273,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AG059236-01A1"],"award-info":[{"award-number":["AG059236-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016400","name":"NRF","doi-asserted-by":"publisher","award":["2018M3C7A1056896"],"award-info":[{"award-number":["2018M3C7A1056896"]}],"id":[{"id":"10.13039\/100016400","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016400","name":"NRF","doi-asserted-by":"publisher","award":["2020R1A2C2010285"],"award-info":[{"award-number":["2020R1A2C2010285"]}],"id":[{"id":"10.13039\/100016400","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common cause of dementia, typically showing progressive neurodegeneration in aging brains. The key signatures of the AD progression are the deposition of amyloid-beta (A\u03b2) peptides, the formation of tau tangles, and the induction of detrimental neuroinflammation leading to neuronal loss. However, conventional pharmacotherapeutic options are merely relying on the alleviation of symptoms that are limited to mild to moderate AD patients. Moreover, some of these medicines discontinued to use due to either the insignificant effectiveness in improving the cognitive impairment or the adverse side effects worsening essential bodily functions. One of the reasons for the failure is the lack of knowledge on the underlying mechanisms that can accurately explain the major causes of the AD progression correlating to the severity of AD. Therefore, there is an urgent need for the better understanding of AD pathogenesis and the development of the disease-modifying treatments, particularly for severe and late-onset AD, which have not been covered thoroughly. Here, we review the underlying mechanisms of AD progression, which have been employed for the currently established therapeutic strategies. We believe this will further spur the discovery of a novel disease-modifying treatment for mild to severe, as well as early- to late-onset, AD.<\/jats:p>","DOI":"10.3390\/ijms21249591","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T09:21:15Z","timestamp":1608110475000},"page":"9591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Therapeutic Targeting Strategies for Early- to Late-Staged Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"21","author":[{"given":"You Jung","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering and Engineering Science, Center for Biomedical Engineering and Science, University of North Carolina, Charlotte, NC 28223, USA"},{"name":"Department of Biological Sciences, Center for Biomedical Engineering and Science, University of North Carolina, Charlotte, NC 28223, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0129-0022","authenticated-orcid":false,"given":"Yen N.","family":"Diep","sequence":"additional","affiliation":[{"name":"Institute of Quantum Biophysics, Department of Biophysics, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419,  Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Tran","sequence":"additional","affiliation":[{"name":"Institute of Quantum Biophysics, Department of Biophysics, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419,  Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-2462","authenticated-orcid":false,"given":"Hansang","family":"Cho","sequence":"additional","affiliation":[{"name":"Institute of Quantum Biophysics, Department of Biophysics, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419,  Korea"},{"name":"Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/S0140-6736(05)67889-0","article-title":"Global Prevalence of Dementia: A Delphi Consensus Study","volume":"366","author":"Ferri","year":"2005","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Patterson, C. 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