Overview: Alzheimer’s Disease
Alzheimer’s Disease (AD) is a chronic neurodegenerative disease affecting an estimated 5.5 million people in the United States (US)1 and over 46 million people worldwide.2
- It is the most common cause of dementia and currently available therapies treat symptoms, not the disease itself which is ultimately fatal.1
- With the world’s aging population, AD is quickly becoming “The Disease of the Century”3, a global epidemic and a socio-economic burden impacting families, social service, and healthcare delivery systems.1
Symptoms of AD generally occur in patients in their mid-60s, though symptoms may occur earlier in patients with familial forms of AD stemming from a genetic predisposition. The disease is initially characterized by progressive memory loss, and then slow progression to severe difficulty in accessing basic brain functions, prompting mental disorders.
Alzheimer’s Disease is a multifactorial disorder that involves several different etiopathological mechanisms ultimately leading to neurodegeneration illustrated at the cellular level by the presence of neurofibrillary tangles composed of the hyper-phosphorylated forms of the protein tau and insoluble β-amyloid plaques. The involvement of multiple pathways in the pathogenesis of AD poses a challenge for drug discovery; however, findings from recent studies suggest that the Wnt signaling pathway plays a central role in neuronal dysfunction in AD and other neurodegenerative diseases.4
- Activation of the Wnt/β-catenin pathway is critical for neuronal development, as well as restoration of adult neurogenesis, neuronal maturation, and synaptogenesis.5
- Wnt signaling was found to regulate brain inflammation6 and promote neuroprotection to toxic amyloid fragments through crosstalk with other signaling cascades.7,8
- Taken together, these findings demonstrate that the Wnt pathway and related signaling mechanisms are potential targets for pharmacological intervention in Alzheimer’s Disease.
- Alzheimer’s Association. 2016 Alzheimer’s Disease Facts and Figures. Alzheimers Dement. 2016;12(4).
- Alzheimer’s Disease International. World Alzheimer’s Report 2015: The Global Impact of Dementia.http://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf. Accessed 10/22/2016.
- Simpson SL. Alzheimer’s: The Disease of the Century. LinkedIn article. Website: https://www.linkedin.com/pulse/alzheimers-disease-century-shelby-l-simpson-basw. Accessed 10/22/16.
- Inestrosa NC, Montecinos-Oliva C, Fuenzalida M. Wnt signaling: role in Alzheimer disease and schizophrenia. J Neuroimmune Pharmacol. 2012;7(4):788-807.
- Varela-Nallar L & Inestrosa NC. Wnt signaling in the regulation of adult hippocampal neurogenesis. Front Cell Neurosci. 2013;7(100):1-11.
- Marchetti B & Pluchino S. Wnt your brain be inflamed? Yes, it Wnt! Trends Mol Med. 2013;19(3):144-56.
- Inestrosa NC, Toledo EM. The role of Wnt signaling in neuronal dysfunction in Alzheimer's Disease. Mol Neurodegener. 2008;3(9):1-6.
- Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014;13(7):533-48.