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Mol Neurodegener. 2018 Dec 12;13(1):64. doi: 10.1186/s13024-018-0299-8.

Advances in developing novel therapeutic strategies for Alzheimer's disease.

Cao J1,2,3, Hou J1,2, Ping J3, Cai D4,5,6.

Author information

1
James J Peters VA Medical Center, Research & Development, Bronx, NY, 10468, USA.
2
Department of Neurology, Alzheimer Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
3
The Central Hospital of The Hua Zhong University of Science and Technology, Wuhan, China.
4
James J Peters VA Medical Center, Research & Development, Bronx, NY, 10468, USA. dongming.cai@mssm.edu.
5
Department of Neurology, Alzheimer Disease Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. dongming.cai@mssm.edu.
6
The Central Hospital of The Hua Zhong University of Science and Technology, Wuhan, China. dongming.cai@mssm.edu.

Abstract

Alzheimer's Disease (AD), the most prevalent neurodegenerative disease of aging, affects one in eight older Americans. Nearly all drug treatments tested for AD today have failed to show any efficacy. There is a great need for therapies to prevent and/or slow the progression of AD. The major challenge in AD drug development is lack of clarity about the mechanisms underlying AD pathogenesis and pathophysiology. Several studies support the notion that AD is a multifactorial disease. While there is abundant evidence that amyloid plays a role in AD pathogenesis, other mechanisms have been implicated in AD such as tangle formation and spread, dysregulated protein degradation pathways, neuroinflammation, and loss of support by neurotrophic factors. Therefore, current paradigms of AD drug design have been shifted from single target approach (primarily amyloid-centric) to developing drugs targeted at multiple disease aspects, and from treating AD at later stages of disease progression to focusing on preventive strategies at early stages of disease development. Here, we summarize current strategies and new trends of AD drug development, including pre-clinical and clinical trials that target different aspects of disease (mechanism-based versus non-mechanism based, e.g. symptomatic treatments, lifestyle modifications and risk factor management).

KEYWORDS:

Alzheimer’s disease; Drug development; Novel therapies; Pre-clinical and clinical trials

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