Beyond Amyloid-β: Reevaluating Its Physiological Role to Find Safe Therapies Against Alzheimer’s Disease

Article type: Article Commentary

Authors: Puzzo, Daniela^{a; b; *}

Affiliations: [a] Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy | [b] Oasi Research Institute-IRCCS, Troina, Italy

Correspondence: [*] Correspondence to: Daniela Puzzo, Department of Biomedical and Biotechnological Sciences, Via Santa Sofia 87 – Torri Biologiche, 95123 Catania, Italy. Tel.: +39 095 4781322/35; E-mail: [email protected].

Abstract: This commentary critically examines the long-standing emphasis on amyloid-β (Aβ)-based therapies in Alzheimer’s disease (AD), despite numerous clinical trial failures. It highlights the urgency to reassess research methodologies and challenges the initiation of anti-Aβ trials in preclinical stages of the disease without conclusive proofs of their safety and efficacy. Instead, a comprehensive approach that considers Aβ’s physiological roles and addresses AD complex nature is suggested, encouraging the idea that clinical trial failures may result from targeting the wrong mechanism. Evidence-based scientific research is needed to advance with AD treatment, moving beyond the current conception of Aβ hypothesis.

Keywords: Amyloid-β, BACE1 inhibitors, clinical trials, physiology

DOI: 10.3233/JAD-240406

Journal: Journal of Alzheimer's Disease, vol. 100, no. 3, pp. 783-786, 2024