Review Article

New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease

Authors: Feng Zhang1,2, Ru-jia Zhong1,2, Cheng Cheng1, Song Li1, Wei-dong Le1,3
1 Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian 116021, China
2 First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim 68167, Germany
3 Institute of Neurology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Medical School of University of Electronic Science and Technology of China, Chengdu 610072, China
Correspondence to: Wei-dong Le: wdle_sibs@163.com,
DOI: 10.1038/s41401-020-00565-5
Received: 30 July 2020
Accepted: 25 October 2020
Advance online: 2 December 2020

Abstract

As the population ages, Alzheimer’s disease (AD), the most common neurodegenerative disease in elderly people, will impose social and economic burdens to the world. Currently approved drugs for the treatment of AD including cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and an N-methyl-D-aspartic acid receptor antagonist (memantine) are symptomatic but poorly affect the progression of the disease. In recent decades, the concept of amyloid-β (Aβ) cascade and tau hyperphosphorylation leading to AD has dominated AD drug development. However, pharmacotherapies targeting Aβ and tau have limited success. It is generally believed that AD is caused by multiple pathological processes resulting from Aβ abnormality, tau phosphorylation, neuroinflammation, neurotransmitter dysregulation, and oxidative stress. In this review we updated the recent development of new therapeutics that regulate neurotransmitters, inflammation, lipid metabolism, autophagy, microbiota, circadian rhythm, and disease-modified genes for AD in preclinical research and clinical trials. It is to emphasize the importance of early diagnosis and multiple-target intervention, which may provide a promising outcome for AD treatment.
Keywords: Alzheimer’s disease; new therapeutics; gut microbiota regulators; anti-inflammatory drugs; lipid metabolism regulators; autophagic modifiers; circadian rhythm regulators; gene and cell therapies

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