Pathogenesis, Animal Models, and Drug Discovery of Alzheimer’s Disease

Article type: Review Article

Authors: Xia, Zhao-Di^{a; 1} | Ma, Ruo-Xin^{a; 1} | Wen, Jin-Feng^a | Zhai, Yu-Fei^a | Wang, Yu-Qi^a | Wang, Feng-Yun^a | Liu, Dan^a | Zhao, Xiao-Long^a | Sun, Bao^{a; b} | Jia, Pu^{a; *} | Zheng, Xiao-Hui^{a; *}

Affiliations: [a] Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, PR China | [b] Department of Pharmacy, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, PR China

Correspondence: [*] Correspondence to: Pu Jia, Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, 710069, Shaanxi, PR China. Tel.: +86 029 88302686; E-mail: [email protected] and Xiao-Hui Zheng, Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi’an, 710069, Shaanxi, PR China. Tel.: +86 029 88302686; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD), the most common cause of dementia, is a chronic neurodegenerative disease induced by multiple factors. The high incidence and the aging of the global population make it a growing global health concern with huge implications for individuals and society. The clinical manifestations are progressive cognitive dysfunction and lack of behavioral ability, which not only seriously affect the health and quality of life of the elderly, but also bring a heavy burden to the family and society. Unfortunately, almost all the drugs targeting the classical pathogenesis have not achieved satisfactory clinical effects in the past two decades. Therefore, the present review provides more novel ideas on the complex pathophysiological mechanisms of AD, including classical pathogenesis and a variety of possible pathogenesis that have been proposed in recent years. It will be helpful to find out the key target and the effect pathway of potential drugs and mechanisms for the prevention and treatment of AD. In addition, the common animal models in AD research are outlined and we examine their prospect for the future. Finally, Phase I, II, III, and IV randomized clinical trials or on the market of drugs for AD treatment were searched in online databases (Drug Bank Online 5.0, the U.S. National Library of Medicine, and Alzforum). Therefore, this review may also provide useful information in the research and development of new AD-based drugs.

Keywords: Alzheimer’s disease, animal model, drug discovery, neurodegenerative, pathogenesis

DOI: 10.3233/JAD-230326

Journal: Journal of Alzheimer's Disease, vol. 94, no. 4, pp. 1265-1301, 2023