Alzheimer's mutations may disrupt nerve-to-muscle connections outside the brain
University of Central Florida researchers found in the lab that mutations linked to inherited Alzheimer's can disrupt nerve signals to muscles even without a brain or spinal cord present. The finding suggests movement problems could be an early sign of the disease.
Scientists at the University of Central Florida (UCF) in the United States have shown, using a human-cell laboratory model, that genetic mutations associated with Alzheimer's disease can directly interfere with the nerves that control muscle movement. This happened even though the system contained no brain or spinal cord. The study, published in Alzheimer's & Dementia, suggests that changes in walking, balance or coordination could be an earlier warning sign than memory problems, and that drugs aimed only at the brain may not fix problems elsewhere in the body.
The research was led by James Hickman, a professor at UCF's Nanoscience Technology Center, and Research Professor Xiufang "Nadine" Guo, together with scientists at the healthcare technology company Hesperos. It was funded by the National Institute on Aging, part of the US National Institutes of Health.
What the researchers did
The team focused on familial Alzheimer's, a rare inherited form that typically appears earlier than the more common form, between ages 40 and 65. Using "human-on-a-chip" technology, which combines different human cell types on a miniature platform, they built a model of the neuromuscular junction, the point where a motor neuron communicates with a muscle cell. The model paired healthy muscle cells with motor neurons derived from stem cells that carried the disease-linked mutations.
The results showed that the mutations could disrupt normal signalling from nerve to muscle. The researchers measured how consistently nerve signals triggered muscle contractions and how long the muscles could keep contracting before tiring.
Implications and limits
Hickman said this is the first demonstration that deficits in the peripheral nervous system can arise directly from these mutations. Guo said that if such changes can be detected and treated earlier, the onset of central nervous system symptoms might be delayed.
The experiments, however, do not establish that these changes necessarily occur before memory loss in patients. Further research is needed to determine how closely the laboratory results reflect the course of Alzheimer's in people, particularly in the more common forms of the disease.
