Summary: New research suggests that the balance and walking issues associated with Alzheimer\u2019s disease may not be \u201ctop-down\u201d problems caused by brain decay, but rather \u201cbottom-up\u201d failures in the peripheral nervous system.<\/p>\n
The study utilized \u201chuman-on-a-chip\u201d technology to prove that genetic mutations for familial Alzheimer\u2019s can damage the connection between nerves and muscles directly, independent of the brain or spinal cord.<\/p>\n
Key Findings<\/p>\n
Beyond the Brain: This is the first time researchers have demonstrated that peripheral nervous system deficits arise directly from Alzheimer\u2019s mutations.Why Medications Fail: Hickman notes that drugs targeting the brain\u2019s \u201cplaques and tangles\u201d may fail to address movement issues if those problems are rooted in the nerves of the limbs.The \u201cHuman-on-a-Chip\u201d Advantage: Traditional animal models often fail to replicate human Alzheimer\u2019s progression. This lab-grown system uses actual human stem cells to recreate biological functions more accurately.The Reflex Connection: The failure at the NMJ is the same circuit tested when a doctor taps your knee with a mallet. In Alzheimer\u2019s patients, this \u201creflex\u201d hardware may be breaking down at a cellular level.<\/p>\n
Source: University of Central Florida<\/p>\n
UCF researchers have uncovered evidence that some movement-related symptoms of Alzheimer\u2019s disease may originate outside the brain, which could change how the disease is diagnosed and treated in the future.<\/p>\n
The study was sponsored by the National Institutes of Health\u2019s National Institute on Aging and was led by UCF Nanoscience Technology Center Professor James Hickman and Research Professor Xiufang \u201cNadine\u201d Guo.<\/p>\n
In collaboration with researchers at healthcare tech company Hesperos, the team used lab-grown, human-cell systems designed to model how the body functions to examined how genetic mutations associated with familial Alzheimer\u2019s affects movement.<\/p>\n
The study was recenty published in\u00a0Alzheimer\u2019s & Dementia: The Journal of the Alzheimer\u2019s Association.\u00a0\u00a0<\/p>\n
\u201cMotor deficits may be an earlier indication [of Alzheimer\u2019s],\u201d she says. \u201cIf we can detect those changes and intervene earlier, that could help delay the onset of central nervous system symptoms.\u201d<\/p>\n
How\u00a0Movement and Alzheimer\u2019s Are Connected<\/p>\n
Familial Alzheimer\u2019s is a rare form of the disease that is hereditary and appears earlier (from 40 to 65 years of age) in people affected than those with the typical condition.\u00a0<\/p>\n
While Alzheimer\u2019s disease is widely associated with memory loss and dementia, clinicians have long observed that some patients show changes in balance, gait (manner of walking) or movement years before cognitive symptoms appear. These early motor changes raise questions about whether parts of the disease begin outside the brain.<\/p>\n
Through a tech-powered approach, the team found that the diseased motor neurons \u2014 even without involvement from the brain \u2014 disrupted the neuromuscular junction, which is central to daily movement.\u00a0<\/p>\n
\u201cThis is the first time it\u2019s been demonstrated that deficits in the peripheral nervous system can arise directly from these mutations,\u201d Hickman says. \u201cIt means drugs that target the brain may not fix problems in the rest of the body.\u201d<\/p>\n
Maintaining motor function may also support overall brain health, as physical activity is known to play a role in cognitive well-being, Guo notes.\u00a0<\/p>\n
How Researchers Build Human Disease Models in the Lab<\/p>\n
To explore how these mutations affect movement, the researchers turned to a cutting-edge approach called \u201chuman-on-a-chip\u201d technology, which is manufactured through Hesperos, a company co-founded by Hickman.<\/p>\n
These miniature lab systems recreate the way human cells interact and function in the body, allowing scientists to study disease in a more realistic way than traditional lab or animal models.<\/p>\n
The team built a neuromuscular junction-on-a-chip \u2014 a small system that mimics the connection between motor neurons and muscle cells. What makes this system powerful is what\u2019s left out: the brain and spinal cord.<\/p>\n
By isolating motor neurons and muscle cells, the researchers could determine whether movement problems could arise without the central nervous system being involved.<\/p>\n
To test this, the researchers paired healthy muscle cells with motor neurons that were created from stem cells and carried familial Alzheimer\u2019s disease mutations. The findings suggest that Alzheimer\u2019s-related movement issues may begin in the network of nerves outside the brain and spinal cord rather than being caused solely by brain degeneration.<\/p>\n
Why the Nerve-to-Muscle Connection Matters<\/p>\n
The neuromuscular junction is the point where a nerve cell signals a muscle to contract, making movement possible. If that connection is damaged, the body may lose strength, coordination or endurance.<\/p>\n
In the study, the researchers measured several aspects of neuromuscular function, including how reliably nerve signals triggered muscle contraction and how long muscles could remain contracted before fatiguing. These measurements mirror the kinds of tests doctors use to evaluate movement disorders.<\/p>\n
\u201cYou can\u2019t move unless the motor circuit works,\u201d Hickman says. \u201cWhen a doctor taps your knee to check your reflex, they\u2019re testing that exact connection.\u201d<\/p>\n
The Future of \u2018Human-on-a-Chip\u2019 Technology<\/p>\n
The researchers believe their approach will become increasingly important as drug developers look for more accurate ways to study human disease.\u00a0<\/p>\n
Because the models use human cells and measure real biological function, they can reveal effects that may not appear in animal studies.\u00a0<\/p>\n
For Hickman, the work reflects 30 years of research to better understand disease and help people.\u00a0<\/p>\n
\u201cThese systems let us study disease in a way that\u2019s closer to what actually happens in the human body, and that\u2019s what we need to develop better treatments,\u201d he says.\u00a0<\/p>\n
Key Questions Answered:Q: Does this mean Alzheimer\u2019s is a muscle disease?<\/p>\n
A: Not exactly. It\u2019s still a neurological disease, but this research shows it affects the entire nervous system, not just the brain. The \u201cwiring\u201d that connects your spine to your legs might be failing just as early as the \u201chard drive\u201d in your head.<\/p>\n
Q: Could physical therapy help treat Alzheimer\u2019s?<\/p>\n
A: The researchers suggest that maintaining motor function may support overall brain health. If we can intervene at the nerve-muscle level early on, we might be able to delay the onset of the more severe cognitive symptoms.<\/p>\n
Q: What is a \u201chuman-on-a-chip\u201d?<\/p>\n
A: It\u2019s a miniature system that uses live human cells grown on a microchip to mimic organ functions. It allows scientists to test how \u201cdiseased\u201d nerves talk to \u201chealthy\u201d muscles without needing a human volunteer or an animal subject.<\/p>\n
Editorial Notes:This article was edited by a Neuroscience News editor.Journal paper reviewed in full.Additional context added by our staff.About this Alzheimer\u2019s disease research news<\/p>\n
Author:\u00a0Margot Winick<\/a>
Source:\u00a0University of Central Florida<\/a>
Contact:\u00a0Margot Winick \u2013 University of Central Florida
Image:\u00a0The image is credited to Neuroscience News<\/p>\n