Overview: Alzheimer’s Disease
Alzheimer’s disease (AD), the most common cause of dementia, is a chronic neurodegenerative disease affecting an estimated 5.8 million people in the United States (U.S.)1 and over 46 million people worldwide.2
- Currently approved therapies help manage some symptoms but do not address the underlying causes or the progression of the disease, which is ultimately fatal.1
- With the world’s aging population, AD is quickly becoming a global epidemic, and a socioeconomic burden impacting families, social services, and healthcare delivery systems.1
Symptoms of AD generally appear 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 followed by slow progression to severe difficulty in accessing basic brain functions and subsequent mental disorders.
Alzheimer’s disease is a multifactorial disorder that involves several different etiopathological mechanisms. These include aggregation and deposition of tau and amyloid that contribute to the neurodegeneration that characterizes AD.
The DYRK1A kinase is a promising target for Alzheimer’s disease research. DYRK1A contributes to the formation of amyloid plaques and may induce inflammation.3,4 In animal models of AD, upregulated DYRK1A activity also causes biochemical modification of tau protein structure in the brain.3-6 Inhibition of DYRK1A activity may reduce tau, amyloid, and related inflammatory pathology, thus providing a potential treatment modality for AD.
- Alzheimer’s Association. 2019 Alzheimer’s Disease Facts and Figures. Alzheimers Dement. 2019;15(3):321-87.
- Alzheimer’s Disease International. World Alzheimer’s Report 2015: The Global Impact of Dementia. http://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf. Accessed 05/29/2019.
- Ryoo SR, Cho HJ, Lee HW, et al. Dual-specificity tyrosine(Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: Evidence for a functional link between Down syndrome and Alzheimer's disease. J Neurochem. 2008;104(5):1333-44.
- Khor B, Gagnon JD, Goel G, et al. The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells. Elife. 2015;4:1-27.
- Wegiel J, Gong CX, Hwang YW. The role of DYRK1A in neurodegenerative diseases. FEBS Journal. 2011;278(2):236-45.
- Ferrer I, Barrachina M, Puig B, et al. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis. 2005;20(2):392-400.