Discovery of Mitochondrial Plaques in Alzheimer’s Disease

Researchers have identified a novel type of brain plaque, named “mitochondrial plaques,” that could reshape the understanding of Alzheimer’s disease development. This discovery, made by the University of Minnesota, may pave the way for new treatment strategies.

Published in Nature Neuroscience, the findings reveal that mitochondrial plaques show up earlier than the well-known beta-amyloid plaques, often considered hallmarks of Alzheimer’s. This disease, marked by the progressive loss of brain cells and cognitive abilities, has traditionally been studied through the lens of beta-amyloid plaques and neurofibrillary tangles.

The newly identified mitochondrial plaques seem to form independently of amyloid plaques and may appear in the earliest stages of the disease. This study highlights that these plaques contain high levels of amyloid precursor protein, the precursor to beta-amyloid. As Alzheimer’s progresses, mitochondrial plaques are commonly found alongside traditional amyloid plaques, suggesting a potential role in the disease’s characteristic brain changes.

This discovery identifies mitochondrial plaques as a previously unrecognized feature of Alzheimer’s disease, said Paul Robbins, a professor at the University of Minnesota Medical School. By understanding how these plaques form and contribute to disease progression, we may develop new strategies to slow or even prevent Alzheimer’s.

Unlike extracellular traditional amyloid plaques, mitochondrial plaques appear to directly impact neurons, making them a potential target for future treatments. Xiuli Dan, the study’s first author, emphasized the significance of this find.

Experts stress the need for more research to comprehend the discovery’s full importance. Laura Bojarskaite, a neuroscientist not involved in the study, noted that if validated, these findings could shift scientists’ understanding of Alzheimer’s onset.

Bojarskaite highlighted that early biological changes do not necessarily cause the disease. A crucial question is whether mitochondrial plaques contribute to neurodegeneration or reflect stressed neurons.

The study also touches on the role of mitochondrial dysfunction in Alzheimer’s. The unclear relationship between mitochondrial problems and disease progression remains an area of interest. Determining why some neurons are particularly vulnerable and if mitochondrial changes are widespread is essential.

The discovery might eventually offer practical benefits. Should future research confirm that mitochondrial plaques form before amyloid plaques, they could serve as early biomarkers for Alzheimer’s. Therapies focusing on mitochondrial function rather than solely on amyloid may emerge.

Bojarskaite urged caution, emphasizing the need for independent replication, observations in living patients, and demonstrated prediction of disease progression before clinical applications can be realized. People should see studies like this as promising, not practice-changing, she advised.

The University of Minnesota’s research team plans to identify biomarkers linked to mitochondrial plaques and screen potential drugs to prevent their accumulation. These efforts aim to determine if these structures have a direct role in Alzheimer’s and if they can be targeted to slow disease progression.

Reference: Xiuli Dan et al., “Mitochondrial accumulation and lysosomal dysfunction result in mitochondrial plaques in Alzheimer’s disease,” Nature Neuroscience (2026). DOI: 10.1038/s41593-026-02390-1