{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T14:53:49Z","timestamp":1794408829646,"version":"4.9.0"},"reference-count":446,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T00:00:00Z","timestamp":1752969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004702","name":"University of Genoa","doi-asserted-by":"publisher","award":["FRA2023"],"award-info":[{"award-number":["FRA2023"]}],"id":[{"id":"10.13039\/501100004702","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive, complex, multifactorial, neurodegenerative disease and accounts for most cases of dementia. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and monoclonal antibodies. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis, having only symptomatic effects. Thus, the priority remains prevention and clarifying AD etiology. A better understanding of the neuroprotective mechanisms undertaken by specific genes is crucial to guide the design of novel therapeutic agents via selective ligands and precision medicine. In this review, we present a perspective of the physiological phase of the AD spectrum, of risk factors in AD with a focus on therapeutic approaches in three categories: neurotransmitters\/ion modulations, peptide deposit control and aspecific treatments, followed by a discussion of treatment limitations. An overview of innovative strategies and non-pharmaceutical ancillary support is given.<\/jats:p>","DOI":"10.3390\/ijms26146980","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T09:33:53Z","timestamp":1753090433000},"page":"6980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Alzheimer\u2019s Disease Etiology Hypotheses and Therapeutic Strategies: A Perspective"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-715X","authenticated-orcid":false,"given":"Naomi","family":"Scarano","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"},{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7228-0086","authenticated-orcid":false,"given":"Francesca","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Casini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"},{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-7726","authenticated-orcid":false,"given":"Chiara","family":"Brullo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1554-429X","authenticated-orcid":false,"given":"Pasqualina","family":"D\u2019Ursi","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-0445","authenticated-orcid":false,"given":"Paola","family":"Fossa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"},{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Schenone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Cichero","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,20]]},"reference":[{"key":"ref_1","unstructured":"Scarano, N. 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