Untangling Alzheimer’s Disease — DNA Damage in Alzheimer’s

Tuesday, September 20, 2016

While new discoveries about Alzheimer’s seem to be published on a daily basis, little progress has been made in finding effective treatments for Alzheimer’s and related dementias. Over a decade has passed since the last drug, memantine, was approved by the FDA to ameliorate the symptoms of Alzheimer’s. Although current drugs alleviate the symptoms of Alzheimer's in some people for a limited time, they do not treat the underlying disease or delay its progression.

Given that Alzheimer’s is such a complex disease with many causes and pathways, it is not surprising that the search for effective treatments has proven difficult. So I spoke with Drs. Yujun Hou and Hyundong Song, postdoctoral fellows in the IRP’s Laboratory of Molecular Gerontology at the National Institute on Aging (NIA) to learn more about their approaches to meeting the challenge.

DNA is damaged in several different ways in patients with Alzheimer’s disease,” Hou explains, “suggesting that the body’s response to DNA damage is deficient and may be exacerbating the progression of Alzheimer’s.”

Drs. Hyundong Song and Yujun Hou, standing together here in their lab, are postdoctoral fellows working to find ways that doctors may one day effectively treat Alzheimer’s disease.

Drs. Hyundong Song and Yujun Hou (left to right) are postdoctoral fellows working to find ways that doctors may one day effectively treat Alzheimer’s disease.

Most current treatment strategies target the abnormal proteins deposited in the brain of Alzheimer's patients—Aβ and tau. While they are important targets for therapies, it is also important to explore novel treatment avenues, given the slow pace of the development for such treatments.

“We believe that drugs that repair DNA could be a novel therapeutic strategy for Alzheimer’s patients,” Song says.

To examine their hypothesis, Dr. Hou turns to a widely-used strain of mice in Alzheimer’s research that contains three mutations (APP Swedish, MAPT P301L, and PSEN1 M146V) associated with familial Alzheimer's—the rare, early-onset form of Alzheimer'sas opposed to the more common ‘sporadic’ Alzheimer’s disease. She treats the mice with drugs that enhance DNA repair, then compares the onset and progression of Alzheimer’s with the trajectory of the disease observed in untreated mice. Since the drug may have multiple effects, their laboratory is assessing a number of factors: changes in vasculature, modified neurotransmitter signaling, the extent of nuclear and mitochondrial DNA damage and repair pathways, the degree of Aβ and tau buildup, and changes in memory and motor function.

Hou and Song are motivated in their research by the growing social and economic toll the disease is taking on our world.

“Treatment is greatly needed,” Hou says. “Targeting DNA repair as a way to treat Alzheimer’s has not yet been widely pursued, so we are very optimistic and excited about its potential.”

References:

Hou, Y., Song, H., Croteau, D. L., Akbari, M., & Bohr, V. A. (2016). Genome instability in Alzheimer disease. Mechanisms of Ageing and Development, 2003. http://doi.org/10.1016/j.mad.2016.04.005

Category: Science

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