{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:56:01Z","timestamp":1791320161377,"version":"4.3.1"},"reference-count":167,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline and neuropathological hallmarks, including amyloid-\u03b2 (A\u03b2) plaques, neurofibrillary tangles (NFTs), and neurodegeneration. Since the amyloid cascade hypothesis was proposed, A\u03b2 has remained a central therapeutic target, with interventions aiming to reduce A\u03b2 production, aggregation, or downstream toxicity. This review first outlines the historical development of the A\u03b2 hypothesis and the two major APP processing pathways (\u03b1-cleavage and \u03b2-cleavage), highlighting the role of biomarkers in early diagnosis, patient stratification, and regulatory approval. We then summarize the development and clinical outcomes of anti-A\u03b2 small-molecule drugs, including \u03b2-secretase inhibitors, \u03b3-secretase modulators, A\u03b2 aggregation inhibitors, receptor\/synapse modulators, and metabolic or antioxidant modalities. We further review the progression of biologic therapies, with a particular focus on monoclonal antibodies, vaccines, and emerging gene-silencing strategies, such as small interfering RNA (siRNA) and antisense oligonucleotides. Finally, we discuss future perspectives, including next-generation biologics, multi-target approaches, optimized delivery platforms, and early-prevention strategies. Collectively, these efforts underscore both the challenges and opportunities in translating anti-A\u03b2 therapies into meaningful clinical benefits for patients with AD.<\/jats:p>","DOI":"10.3390\/brainsci15101101","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:13:27Z","timestamp":1760361207000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Therapeutic Advances in Targeting the Amyloid-\u03b2 Pathway for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Beiyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Molecular Therapeutics and Formulations, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunan","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapeutics and Formulations, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7090-2221","authenticated-orcid":false,"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapeutics and Formulations, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2112-0510","authenticated-orcid":false,"given":"Xinai","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapeutics and Formulations, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2135-3812","authenticated-orcid":false,"given":"Zheying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Molecular Therapeutics and Formulations, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-med-042915-103753","article-title":"Update on Alzheimer\u2019s Disease Therapy and Prevention Strategies","volume":"68","author":"Graham","year":"2017","journal-title":"Annu. 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