Alzheimer's disease is best known for its effects on memory and thinking, but new research suggests that some symptoms may develop in a surprising place: outside the brain. Scientists at the University of Central Florida (UCF) have discovered that genetic mutations associated with Alzheimer's can interfere with the nerves that control muscle movement, even without involvement from the brain or spinal cord. The findings could help explain why some people with Alzheimer's experience changes in walking, balance, or coordination long before noticeable memory problems emerge.
The discovery raises the possibility that movement difficulties could provide earlier warning signs of the disease and that treatments focused exclusively on the brain may overlook important 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, working alongside scientists at the healthcare technology company Hesperos. Funded by the National Institutes of Health's National Institute on Aging, the study used laboratory systems built from human cells to investigate how inherited Alzheimer's mutations affect movement.
The findings were published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. "Motor deficits may be an earlier indication [of Alzheimer's]," Guo says. "If we can detect those changes and intervene earlier, that could help delay the onset of central nervous system symptoms." Why Alzheimer's Symptoms May Appear Before Memory Loss Alzheimer's is generally associated with progressive memory loss, confusion, and declining cognitive abilities.
However, doctors have also observed that some patients develop physical symptoms, including changes in balance, coordination, and gait (manner of walking), years before clear cognitive difficulties become apparent. These observations have raised an important question: Are such movement problems simply a consequence of damage occurring in the brain, or could Alzheimer's also interfere directly with nerves elsewhere in the body? To investigate, the UCF team focused on familial Alzheimer's, a rare inherited form of the disease that typically develops earlier in life (from 40 to 65 years of age) than the more common form.
Their experiments revealed that motor neurons carrying mutations linked to familial Alzheimer's could disrupt the connections responsible for controlling muscles, even when the brain and spinal cord were completely absent from the experimental system. Motor neurons are specialized nerve cells that transmit signals to muscles, telling them when to contract and produce movement. The new findings suggest that Alzheimer's mutations can interfere with this process directly, rather than affecting movement only through damage to the brain.
"This is the first time it's been demonstrated that deficits in the peripheral nervous system can arise directly from these mutations," Hickman says. "It means drugs that target the brain may not fix problems in the rest of the body." The peripheral nervous system includes the nerves located outside the brain and spinal cord. These nerves carry signals between the central nervous system and the rest of the body, helping control movement, sensation, and other essential functions.
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