Newly Identified Mitochondrial Plaques Offer a Potential Alzheimer’s Treatment Target

A University of Minnesota research team has identified a type of plaque that represents a new potential therapeutic target for Alzheimer’s disease. The findings were recently published in Nature Neuroscience. 

Alzheimer's disease is a devastating neurodegenerative disorder affecting millions of individuals worldwide. Scientists have long known that two hallmarks of the disease are beta-amyloid (Aβ) plaques and neurofibrillary tangles, which damage and kill brain cells over time.

The researchers identified a newly recognized type of brain plaque, called mitochondrial plaques, in both preclinical models of Alzheimer's disease and human brain tissue. Mitochondrial plaques appear to form independently of traditional amyloid plaques and may emerge at the earliest stages of the disease, possibly even before beta-amyloid plaques begin to develop.

The researchers also found that mitochondrial plaques contain high levels of amyloid precursor protein, which is the molecule that gives rise to beta-amyloid. As the disease progresses, mitochondrial plaques frequently appear alongside traditional amyloid plaques, suggesting they may help drive the formation of those hallmark brain changes.

“This discovery identifies mitochondrial plaques as a previously unrecognized feature of Alzheimer's disease,” said Paul Robbins, PhD, professor in the University of Minnesota Medical School and associate director of the Masonic Institute on the Biology of Aging and Metabolism. “By understanding how these plaques form and contribute to disease progression, we may be able to develop new strategies to slow or even prevent Alzheimer's disease.”

“Unlike the amyloid plaques found outside brain cells, these plaques appear to directly affect neurons, which make them a potential new target for Alzheimer’s disease treatments,” said Xiuli Dan, first author and research assistant professor. 

Next steps include the identification of biomarkers of mitochondrial plaques and screening for drugs that can prevent their accumulation.