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BioMed Research International
Volume 2014 (2014), Article ID 301575, 9 pages
Review Article

The Role of Wnt Signaling in the Development of Alzheimer’s Disease: A Potential Therapeutic Target?

1Geriatrics Department of Traditional Chinese Medicine, Huadong Hospital, Fudan University, Shanghai 200040, China
2Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai 200040, China
3Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women’s Hospital, Parkville, VIC 3052, Australia

Received 12 October 2013; Accepted 10 April 2014; Published 4 May 2014

Academic Editor: Raymond Chuen-Chung Chang

Copyright © 2014 Wenbin Wan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Accumulating evidence supports a key role for Wnt signaling in the development of the central nervous system (CNS) during embryonic development and in the regulation of the structure and function of the adult brain. Alzheimer’s disease (AD) is the most common form of senile dementia, which is characterized by β-amyloid (Aβ) deposition in specific brain regions. However, the molecular mechanism underlying AD pathology remains elusive. Dysfunctional Wnt signaling is associated with several diseases such as epilepsy, cancer, metabolic disease, and AD. Increasing evidence suggests that downregulation of Wnt signaling, induced by Aβ, is associated with disease progression of AD. More importantly, persistent activation of Wnt signaling through Wnt ligands, or inhibition of negative regulators of Wnt signaling, such as Dickkopf-1 (DKK-1) and glycogen synthase kinase-3β (GSK-3β) that are hyperactive in the disease state, is able to protect against Aβ toxicity and ameliorate cognitive performance in AD. Together, these data suggest that Wnt signaling might be a potential therapeutic target of AD. Here, we review recent studies related to the progression of AD where Wnt signaling might be relevant and participate in the development of the disease. Then, we focus on the potential relevance of manipulating the Wnt signaling pathway for the treatment of AD.