Scientists have discovered a previously unknown type of brain plaque, which might lead to advancements in understanding Alzheimer’s disease and suggest new treatment approaches. This breakthrough, reported by researchers at the University of Minnesota, involves “mitochondrial plaques,” newly identified features of Alzheimer’s found in both preclinical disease models and human brain tissues. Findings published in Nature Neuroscience indicate these plaques could appear earlier than the widely recognized beta-amyloid plaques, long associated with the disease.
Alzheimer’s is marked by the progressive loss of brain cells and cognitive decline. For years, research has focused on beta-amyloid plaques and neurofibrillary tangles that build up in the brain during disease progression. The newly found mitochondrial plaques seem to form independently from traditional amyloid plaques and may manifest at the earliest stage of the condition.
Researchers found mitochondrial plaques contain high levels of amyloid precursor protein, which forms beta-amyloid. As Alzheimer’s progresses, these plaques frequently appear alongside traditional amyloid plaques, leading scientists to propose that they might contribute to the disease’s classic brain alterations.
Paul Robbins, a professor at the University of Minnesota Medical School, stated, “This discovery identifies mitochondrial plaques as a previously unrecognized feature of Alzheimer’s disease. By understanding how these plaques form and contribute to disease progression, we may develop new strategies to slow or even prevent Alzheimer’s disease.” Unlike traditional plaques found outside brain cells, the newly identified plaques seem to directly impact neurons, offering a possible new target for treatment according to Xiuli Dan, a research assistant professor and first author of the study.
These findings suggest Alzheimer’s-related changes could commence earlier and via different biological pathways than previously believed. However, experts emphasize the need for more research to fully comprehend the significance. Laura Bojarskaite, a neuroscientist at the University of Oslo, noted that should the findings be confirmed, they could redefine the understanding of how Alzheimer’s begins. She warned, though, that early biological changes do not necessarily cause the disease.
The study touches on mitochondrial dysfunction’s role in Alzheimer’s research. While it is acknowledged that mitochondria often malfunction in Alzheimer’s, Bojarskaite pointed out it remains uncertain whether such issues trigger the disease or result from other ongoing changes. Researchers must understand why certain neurons are particularly vulnerable and if mitochondrial alterations are common or only one pathway in a complex disease.
Discovery of mitochondrial plaques could have practical implications if future research validates that they form before traditional amyloid plaques. They could serve as biomarkers for early identification of at-risk individuals, allowing for timely interventions. The results might also inspire therapies that focus on preserving mitochondrial function rather than solely targeting amyloid. However, Bojarskaite stressed that challenges remain. Findings need independent replication, observation in living patients, and demonstrated ability to predict disease progression before clinical application is possible. “People should see studies like this as promising, not practice-changing,” Bojarskaite said.
The University of Minnesota researchers plan to identify biomarkers associated with mitochondrial plaques and test drugs to prevent their formation. This work aims to clarify whether the newly discovered structures play a direct role in Alzheimer’s and whether targeting them can 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