University of Minnesota researchers have identified what they're calling "mitochondrial plaques" — a newly recognized buildup inside neurons that's distinct from the beta-amyloid plaques that have dominated Alzheimer's research for decades. The findings, published July 29 in Nature Neuroscience, were led by research assistant professor Xiuli Dan and senior author Paul Robbins, a professor in the Medical School and associate director of the university's Masonic Institute on the Biology of Aging and Metabolism.
Unlike traditional amyloid plaques, which sit outside cells, the mitochondrial plaques form directly inside neurons and carry high levels of amyloid precursor protein — the same molecule that produces beta-amyloid. The team traced their formation to a breakdown in mitophagy, the process cells normally use to clear out damaged mitochondria, combined with malfunctioning lysosomes, the cell's cleanup machinery. Researchers found the plaques in both preclinical disease models and human brain tissue, and say they can appear independently of amyloid plaques, possibly at an earlier stage of the disease, then accumulate alongside them as Alzheimer's progresses.
"This discovery identifies mitochondrial plaques as a previously unrecognized feature of Alzheimer's disease," Robbins said. Dan added that because the plaques act directly on neurons, they represent "a potential new target for treatments." Robbins said understanding how the plaques form and drive disease "may be able to develop new strategies to slow or even prevent Alzheimer's disease."
The study was funded by grants from the National Institute on Aging and a National Academy of Medicine Healthy Longevity Catalyst Award. The researchers said their next steps are identifying biomarkers that could flag mitochondrial plaques in living patients and screening candidate drugs aimed at preventing the buildup before it starts — work that could open a treatment avenue distinct from the anti-amyloid drugs that have so far shown limited success against the disease.