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2018 Alzheimer's Association Research Grant (AARG)

Mechanisms of mitochondrial clearance and Tau accumulation

 
Could removing damaged structures inside nerve cells, prevent tau tangles from forming during Alzheimer’s?
 

Fang Du
University of Kansas
Lawrence, KS - United States



Background

Tau protein normally helps maintain structure and transport nutrients inside nerve cells. During all tauopathies, tau can become modified and form “tangles” that can harm nerve cells. Tau tangles can disrupt how nerve cells function, including how specialized structures inside nerve cells, called mitochondria, make energy for cells. Mitochondria dysfunction inside nerve cells is one of the earliest signs of Alzheimer’s. Targeting enzymes that help protect or maintain healthy mitochondria may be one way to preserve nerve cell function during Alzheimer’s.
 

Research Plan

Dr. Fang Du and colleagues are studying whether removing damaged mitochondria from nerve cells could help delay or slow Alzheimer’s  progression. First, the researchers will assess the effect of harmful tau on mitochondria function in nerve cells growing in laboratory dishes. Dr. Du will then genetically modify mice to increase levels of an enzyme responsible for mitochondria quality control and clearance inside nerve cells (called PTEN-induced putative kinase 1, or “PINK1”). Finally, the researchers will measure tau protein accumulation in these animals. Dr. Du’s team believes that higher levels of PINK1 inside nerve cells could help remove damaged mitochondria and limit tau tangles from forming in genetically engineered Alzheimer’s-like mice.
 

Impact

If successful, this study could identify a new therapeutic avenue for limiting the harmful effects of tau protein during Alzheimer’s. PINK1 could represent a new target for drug developers interested in preserving mitochondria function during Alzheimer’s. The study may also provide additional information about how tau protein damages mitochondria and contributes to nerve cell death.
 

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