Research Project: Determining the contributions of age and neuroinflammation on the pathological conversion of tau
The CART Fund will award Tong Li, Ph.D., Johns Hopkins University School of Medicine, a 2017 research grant in the amount of $75,000. The grant will be awarded on May 9, 2017 at the Annual meeting of The CART Fund in Columbia, SC.
Alzheimer’s disease (AD), the most common form of dementia and a devastating illness for the elderly, is characterized by built-up of clumped proteins observed inside (called tau aggregates) and outside (called amyloid-beta (Aβ) plaques) of nerve cells that lead to memory problems and eventual loss of these cells. Past and current efforts have been focused on finding drugs that could treat either the amyloid or tau problem. Figuring out how these two types of clumped proteins worked together to cause nerve cells to die may hold the key towards finding a solution for AD.
Recently, we established a new mouse model of AD that exhibits accelerated loss of nerve cells due to the built up of clumps of both Aβ and tau. This new mouse model will be valuable for further studying the basis of AD and for screening of drugs that can provide effective therapies for AD. Using this mouse model, we showed that Aβ plaques (outside of nerve cells) facilitate the aggregation of the tau (inside of nerve cells). However, our results indicate that Aβ plaque alone is not sufficient for the built up of tau aggregates. A second risk factor (such as, expression of a fragment of human tau protein) is required to drive the built-up of tau aggregates. Thus, we envision that a combination of risk factors facilitates built-up of tau to drive loss of nerve cells in AD, an idea that can be tested directly in our novel mouse model.
We consider age and inflammation as potential risk factors that drive the built-up of tau aggregates. Among the known risk factors of AD, age is the greatest risk factor and a fundamental driver for development of the disease. AD is also characterized by an inflammatory response. Therefore, we hypothesize that age and inflammatory response facilitate the built-up of tau aggregates to drive nerve cell loss and cognitive decline in AD. We will test this hypothesis using our new mouse model. Resolution of these questions will impact our view regarding disease mechanisms and identification of targets for novel therapeutic strategies for AD.
The Coins for Alzheimer’s Research Trust Fund (CART) is a project of the Rotary Clubs of North America. Founded in 1995 in Sumter SC, CART provides financial support for Alzheimer’s research projects that are yet to be supported by extensive preliminary data but have the potential to substantially advance biomedical research. Learn more at www.cartfund.org