{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:06:17Z","timestamp":1792789577007,"version":"4.5.0"},"reference-count":207,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T00:00:00Z","timestamp":1694217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In an ever-increasing aged world, Alzheimer\u2019s disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of \u03b2-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against A\u03b2 plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment.<\/jats:p>","DOI":"10.3390\/ijms241813900","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:00:52Z","timestamp":1694422852000},"page":"13900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Treatment of Alzheimer\u2019s Disease: Beyond Symptomatic Therapies"],"prefix":"10.3390","volume":"24","author":[{"given":"Francesca R.","family":"Buccellato","sequence":"first","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8625-6506","authenticated-orcid":false,"given":"Marianna","family":"D\u2019Anca","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca Martino","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7144-0984","authenticated-orcid":false,"given":"Massimo","family":"Del Fabbro","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elio","family":"Scarpini","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-5953","authenticated-orcid":false,"given":"Daniela","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jalz.2015.07.214","article-title":"S3-01-01: Prevention report from Alzheimer\u2019s disease international (ADI)","volume":"11","author":"Prince","year":"2015","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12385","DOI":"10.1002\/trc2.12385","article-title":"Alzheimer\u2019s disease drug development pipeline: 2023. 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