Study Finds Alzheimer's Mutations May Affect Peripheral Nerves

Alzheimer’s mutations may disrupt muscle control directly

Genetic mutations linked to Alzheimer’s disease can interfere with the nerves that control muscle movement even without involving the brain or spinal cord, according to new research reported by Science Daily.

While the disease is most commonly associated with memory loss and cognitive decline, scientists at the University of Central Florida (UCF) have found that these mutations may affect the peripheral nervous system. This discovery suggests that changes in walking, balance, or coordination could serve as early warning signs of the disease, appearing long before noticeable memory problems emerge.

The research, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, focused on familial Alzheimer’s. This rare, inherited form of the disease typically manifests in individuals between the ages of 40 and 65.

By using a specialized laboratory system, the team demonstrated that motor neurons—the cells responsible for transmitting signals from the nervous system to the muscles—can be disrupted by these specific genetic mutations independently of the central nervous system.

The neuromuscular connection

Every voluntary movement relies on a precise electrical and chemical exchange at the neuromuscular junction. This is the point where a motor neuron communicates with a muscle cell to trigger a contraction.

When this connection is impaired, muscles may not respond effectively to nerve signals. This can lead to physical symptoms such as weakness, reduced coordination, and difficulty maintaining balance or posture.

James Hickman, a professor at UCF’s Nanoscience Technology Center, noted that these findings change how we view the scope of the disease’s impact.

“This is the first time it’s been demonstrated that deficits in the peripheral nervous system can arise directly from these mutations,” Hickman said. “It means drugs that target the brain may not fix problems in the rest of the body.”

The study highlights a critical gap in current therapeutic approaches. Because many existing Alzheimer’s treatments are designed exclusively to address processes within the brain, they may fail to correct abnormalities occurring in the peripheral nerves and muscles.

Human-on-a-chip technology

To observe these interactions, the researchers utilized “human-on-a-chip” technology, a platform manufactured by Hesperos, a company co-founded by Hickman. These miniature systems allow scientists to recreate biological functions using human cells rather than relying solely on animal models, which do not always mirror human disease progression accurately.

The UCF team created a miniature model of the neuromuscular junction that deliberately excluded the brain and spinal cord. They combined healthy muscle cells with motor neurons derived from stem cells that carried mutations associated with familial Alzheimer’s.

The results showed that the altered nerve cells struggled to communicate effectively with the healthy muscle tissue. The researchers measured how consistently nerve signals produced contractions and how long the muscles could work before fatiguing.

Xiufang “Nadine” Guo, a research professor at UCF, suggested that identifying these physical changes could change the timeline of medical intervention.

“Motor deficits may be an earlier indication [of Alzheimer’s],” Guo said. “If we can detect those changes and intervene earlier, that could help delay the onset of central nervous system symptoms.”

Protecting motor function may also provide a secondary benefit for brain health. Regular physical activity is a known factor in maintaining cognitive well-being, creating a potential feedback loop where preserving movement helps support the brain.

Implications for early detection

The findings suggest that future diagnostic protocols might expand to include physical assessments. Tests for walking patterns, coordination, or nerve-to-muscle activity could eventually help identify disease-related changes before cognitive symptoms become apparent.

However, the researchers cautioned that these laboratory results do not yet prove that movement changes definitely occur before memory loss in human patients. Further studies are required to determine how closely these cellular findings reflect the actual progression of the disease in people, particularly those with the more common, non-familial forms of Alzheimer’s.

Beyond Alzheimer’s, the use of human-on-a-chip systems offers a broader potential for drug development. These platforms allow researchers to observe how treatments affect the interactions between different tissue types, potentially identifying the limitations of a drug earlier in the development process.