Alzheimer’s disease, a condition that gradually erodes memory and independence, remains a formidable challenge for medical science. While current medications can alleviate symptoms, they have yet to stop the disease’s relentless progression. Traditionally, research has focused on the brain, particularly on clearing the sticky protein plaques associated with dementia. However, a groundbreaking study now suggests that an unexpected ally might be found in the body’s muscles.
Researchers from Florida Atlantic University and the University of Copenhagen have discovered that a protein released by active muscles can protect memory and maintain brain health in mice engineered to develop Alzheimer’s-like symptoms. This study, published in the journal Aging Cell, indicates that the path to preserving cognitive function may involve the body as much as the mind.
Unveiling the Role of Cathepsin B
The protein in question is Cathepsin B, or Ctsb. Although it has a controversial reputation due to its presence in cancer and brain injury, Ctsb also functions as a “myokine,” a signaling molecule produced by muscle. In humans, Ctsb levels increase following exercise or electrical muscle stimulation, and higher levels have been correlated with improved cognitive function.
Turning Exercise into Biology
It is well-known that physical activity enhances mood and cognitive sharpness. What is less understood is the extent to which muscles communicate with the brain. When muscles are active, they release signals that travel through the bloodstream, altering brain function. Researchers aimed to replicate this communication without requiring animals to engage in physical training.
Henriette van Praag, an associate professor at Florida Atlantic University and a member of the FAU Stiles-Nicholson Brain Institute, led a team that adopted a novel approach. Instead of making mice exercise, they used gene therapy to increase Ctsb levels directly in muscle tissue.
“Our study is the first to show that expressing Cathepsin B specifically in muscle can prevent memory loss and maintain brain function in a mouse model of Alzheimer’s disease,” van Praag stated.
Experimental Findings and Implications
The research employed a standard Alzheimer’s mouse model known as APP/PS1, which develops plaque buildup, brain inflammation, and memory issues as it ages. At four months old, before severe symptoms appeared, the mice were administered a harmless virus carrying the Ctsb gene, designed to activate primarily in skeletal muscle. A control group received a “blank” virus for comparison.
What the Mice Revealed
By ten months, the differences were striking. Mice with Alzheimer’s that received the muscle treatment performed better in water maze tests, locating hidden platforms more quickly and remembering locations after a day. They also displayed more normal responses in fear tests.
Moreover, these mice exhibited improved motor skills. Untreated animals struggled with balance tasks, while those with elevated Ctsb levels in their muscles performed comparably to healthy controls. The hippocampus, a brain region crucial for learning, showed increased production of new nerve cells in treated mice, counteracting the disease’s tendency to reduce neurogenesis.
Interestingly, the therapy did not clear amyloid plaques or reduce overactive immune cells, yet memory improved regardless. “To see behavior recover while plaques stayed the same was surprising,” a researcher noted.
Broader Implications and Future Directions
The study highlights a new target for dementia therapy: skeletal muscle. Instead of solely focusing on brain plaques, researchers might explore ways to enhance beneficial muscle signals. This could eventually lead to treatments that increase or mimic muscle proteins like Ctsb without relying on gene therapy.
However, the research is still in its early stages. Only male mice were studied, and the sample sizes were small. Different Alzheimer’s models may react differently, and what works in mice does not always translate to humans. Additionally, since healthy mice showed adverse reactions, any future therapy would require precise control to avoid harming healthy brains.
Nonetheless, the findings underscore the importance of regular exercise, not just for cardiovascular health but also for cognitive well-being. Muscle health might be one of the best defenses against brain disease, and exercise programs for older adults could be designed to protect both body and mind.
“Muscle is not just a mechanical tissue,” said Atul S. Deshmukh, an associate professor at the University of Copenhagen. “It is a powerful communicator with the brain.”
For scientists, this research opens new avenues for studying the body as an integrated network rather than isolated organs. The interactions between muscle, blood, and liver could significantly influence brain health.
The study’s findings are available online in the journal Aging Cell, offering a fresh perspective on the potential for muscle-based interventions in Alzheimer’s treatment.
