Researchers at Massachusetts General Hospital have identified a link between irisin, a hormone released during physical activity, and a reduction in brain plaque associated with Alzheimer’s disease. The findings appear in the journal Neuron and add to a growing body of evidence that exercise-related molecules may influence neurodegenerative processes.
Alzheimer’s disease is characterized by the buildup of beta-amyloid protein, which forms plaques in the brain. Earlier work in animal models showed that exercise can lessen beta-amyloid deposits, suggesting that circulating factors produced by muscles during activity might mediate this effect. Irisin, a hormone that helps regulate glucose and lipid metabolism in fat tissue and enhances overall energy expenditure, has emerged as a potential mediator of this protective effect. Observations from patients with dementia have noted lower levels of certain hormones, prompting further exploration into how hormonal changes relate to disease progression.
To explore whether there is a cause-and-effect relationship between reduced beta-amyloid and physical activity, the researchers used a three-dimensional human cell culture system they developed to model Alzheimer’s disease. They treated the cultured cells with irisin and observed a meaningful decline in beta-amyloid deposits. This reduction coincided with an increase in neprilysin activity, an enzyme produced by astrocytes in the brain that can break down beta-amyloid, potentially helping to clear toxic proteins from neural tissue. This dual finding links irisin exposure to both lower plaque formation and enhanced clearance mechanisms.
Earlier experiments in mice demonstrated that when irisin is introduced into the bloodstream, it can cross into the brain, which raises the possibility that irisin or irisin-inspired therapies could be pursued as a treatment strategy for Alzheimer’s disease in humans. The current work therefore provides a plausible biological pathway through which exercise-related signals might influence nerve cell health and plaque dynamics.
Alongside these insights, researchers note that a variety of ongoing studies aim to translate molecular and cellular observations into practical diagnostic or therapeutic approaches. For example, conceptual work in the field includes the development of blood-based diagnostics that could aid early detection of Alzheimer’s disease and guide treatment decisions. The emerging picture is that physical activity, through molecular messengers like irisin, may play a more complex role in brain health than previously understood, offering potential avenues for intervention and prevention.
Citation: Massachusetts General Hospital, Neuron. The broader research program continues to investigate how muscle-derived signals influence brain biology and how such signals could be leveraged to slow or alter the course of neurodegenerative diseases. Additional studies are exploring how biomarkers and therapeutic peptides related to irisin might be integrated into clinical practice in the future. The current findings contribute to a growing consensus that systemic factors generated by exercise can have meaningful effects on brain pathology and function. Citation: Massachusetts General Hospital, Neuron.