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2020 Alzheimer's Association Clinician Scientist Fellowship (AACSF)

Neuropathologic Evaluation of the Role of LRRK2 in Alzheimer's Disease

Could a genetic risk factor for Parkinson’s disease also impact brain changes in Alzheimer’s?

Anne Hiniker, M.D., Ph.D.
University of California
La Jolla, CA - United States



Background

Alzheimer’s and Parkinson’s are considered distinct diseases, but scientists believe they may share common biological mechanisms. Studies have shown some people with Alzheimer’s also have brain changes more commonly associated with Parkinson’s, including one of the hallmarks of the disease, the presence of Lewy bodies. Lewy bodies are halo-like structures comprised of an abnormally shaped protein called alpha synuclein.

Researchers have shown that variations in the gene providing instructions for the protein leucine-rich repeat kinase 2 (LRRK2) can increase a person’s risk of developing Lewy bodies in Parkinson’s disease. Dr. Anne Hiniker believes that if  LRRK2 also plays a role in brain changes in Alzheimer’s, current experimental drugs designed to target LRRK2 in Parkinson’s might be repurposed to treat individuals with (or at risk of developing) Alzheimer’s.
 

Research Plan

Dr. Anne Hiniker and colleagues will study whether LRRK2 impacts brain changes in Alzheimer’s. The researchers will compare the levels and activity of LRRK2 in brain tissue donated by cognitively unimpaired people and people who had Alzheimer’s a) with and b) without Lewy Bodies in their brains. Dr. Kiniker’s goal is to assess whether people with Alzheimer’s and Lewy’s bodies have higher LRRK2 activity in their brains. They will also study whether this activity could possibly be blocked by experimental therapy intended to treat Parkinson’s. Dr. Kiniker’s team will develop tools to directly view LRRK2 in brain tissue samples using specialized microscopes.

Impact

If successful, this study could identify a common mechanism that underlies brain changes seen in both Alzheimer’s and Parkinson’s disease. The findings could lead to clinical trials designed to assess whether Parkinson’s drugs may be repurposed to tackle Alzheimer’s and vice-versa.

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