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2022 Alzheimer's Association Research Fellowship (AARF)

Propagation of Mitochondrial Dysfunction in the Brain by Mitovesicles

Can tiny, pouch-like structures in the brain cause damage to the powerhouse of the cell ?

Pasquale D'Acunzo, Ph.D.
Nathan Kline Institute
Menands, NY - United States



Background

Alzheimer’s is associated with hallmark brain changes including the accumulation of the proteins beta-amyloid and tau into abnormal plaques and tangles, respectively. Alzheimer’s is a complex disease and there are other brain changes that occur.  Recent studies suggest that specialized structures inside cells called mitochondria — the powerhouse of energy generation for the cells — may also undergo damage early on in Alzheimer's, before the development of the plaques and tangles. However, it remains unclear exactly how damaged mitochondria may be linked to these brain changes.

In initial studies, Dr. Pasquale D’Acunzo and colleagues studied a weries specialized brain structures called vesicles. These vesicles are free-floating pouches that can be produced and released by nerve cells to help the cells communicate with one another. Using state-of-the-art scanning techniques, the researchers discovered a type of vesicle called “mitovesicles”, which are produced only by mitochondria. When examining cells in a laboratory dish that had damaged mitochondria, they found that the cells had high levels of mitovesicles. These findings suggest mitovesicles may play a negative role on mitochondria health and may be seen in the early stages of dementia.

Research Plan

Using genetically engineered Alzheimer’s-like mice, Dr. D’Acunzo and team will examine how mitovesicles function in the brain with Alzheimer’s related brain changes and how the mitovesicles may be associated with early-stage mitochondrial damage seen in Alzheimer’s. They will then conduct similar studies to explore the function of mitovesicles on (1) nerve cells and astrocytes (a type of helper cell in the brain) grown in a laboratory dish that have been injected with mitovesicles and (2) living brains of Alzheimer’s-like mice that have also received mitovesicle injections.    

Impact

This study will be among the first to explore the possible role of mitovesicles in dementia. If successful, this study could shed new light on the underlying biology related to mitochondria changes in disease. This may open up the door to new paths for therapy development or developing a way to measure early disease related brain changes for detection and diagnosis. 

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