Targeting Amyloid-β Proteins as Potential Alzheimer's Disease Therapeutics: Anti-Amyloid Drug Discovery, Emerging Therapeutics, Clinical Trials and Implications for Public Health.
Asaad Abdulrahman Abduljawad, Khadijah B Alkinani, Aysha Zaakan, Abeer S AlGhamdi, Alashary Adam Eisa Hamdoon, Batool H Alshanbari, Ahmed Abdullah Alshehri, Badria Bakheet Alluhaybi, Shahad Othman Ibrahim Alqashi, Ryan Abdulrahman Abduljawad
Abstract
Open AccessAlzheimer's disease (AD), a neurodegenerative disorder of the aging brain, is associated with behavioral and cognitive issues and poses a huge burden on the global health care system. One of the key features of AD is the deposition of abnormal proteins called amyloid-beta (Aβ) in the brain, causing inflammatory changes, oxidative stress, and neuronal loss. Recent advancements in the anti-Aβ therapies have considerably improved the management of AD, resulting in better clinical outcomes for patients and caregivers. This review offers an inclusive update on current drug discovery efforts, innovative approaches, and ongoing clinical trials targeting Aβ, a key player in AD pathogenesis. We have evaluated the most recent developments in monoclonal antibodies, including aducanumab (discontinued November 2024), lecanemab, and donanemab, emerging therapeutic options, as well as emerging strategies such as tau-targeting therapies, gene therapy, and small molecule inhibitors. Moreover, we highlighted the challenges and opportunities in AD research, including the need for early diagnosis, personalized medicine, and combination therapies. Our review will offer a concise and informative overview of the current landscape and future directions in anti-Aβ therapeutics for AD, shedding light on potential treatments and prospects for improving patient outcomes.