麻豆原创 researchers聽have聽uncovered聽evidence聽that some movement-related symptoms聽of聽Alzheimer鈥檚 disease聽may originate outside the brain, which could change how聽the disease聽is diagnosed and treated in the future.
The聽study was sponsored by the聽National Institutes of Health鈥檚 National Institute on Aging聽and聽was led by 麻豆原创 Nanoscience Technology Center聽Professor聽James Hickman聽and聽Research聽Professor聽Xiufang 鈥淣adine鈥� Guo. In collaboration with聽researchers at聽healthcare tech company Hesperos, the team used聽lab-grown,聽human-cell systems designed to model how the body functions聽to聽examined聽how genetic mutations associated with聽familial聽Alzheimer鈥檚聽affects聽movement.聽Today, the聽study was published in聽Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
鈥淢otor deficits may be an earlier indication聽[of Alzheimer鈥檚],鈥� she聽says. 鈥淚f we can detect those changes and intervene earlier, that could help delay the onset of central nervous system symptoms.鈥�
How聽Movement and Alzheimer鈥檚 Are Connected
Familial Alzheimer鈥檚 is聽a聽rare聽form of the disease that聽is聽hereditary and appears聽earlier聽(from聽40 to 65 years of age)聽in people affected than those聽with the typical聽condition.
While聽Alzheimer鈥檚 disease is widely聽associated with聽memory loss and dementia,聽clinicians have long聽observed聽that some patients show changes in balance, gait聽(manner of walking)聽or movement years before cognitive symptoms appear. These聽early motor changes聽raise聽questions about whether聽parts of the disease begin聽outside the brain.
Through a tech-powered approach, the聽team found that the diseased motor neurons聽鈥斅爀ven without involvement from the brain聽鈥斅燿isrupted聽the neuromuscular junction, which is聽central to daily movement.
鈥淭his is the first time it鈥檚 been demonstrated that deficits in the peripheral nervous system can arise directly from these mutations,鈥� Hickman聽says. 鈥淚t means drugs that target the brain may not fix problems in the rest of the body.鈥�
Maintaining聽motor function may also聽support overall聽brain聽health,聽as聽physical activity is known to聽play a role in cognitive well-being, Guo notes.
How Researchers Build Human Disease Models in the Lab
To explore how these mutations affect movement, the researchers turned to a聽cutting-edge聽approach called 鈥渉uman-on-a-chip鈥� technology, which is manufactured聽through Hesperos, a company co-founded by Hickman.聽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.
The team built a neuromuscular junction-on-a-chip 鈥� a small system that mimics the connection between motor neurons and muscle cells.聽What makes聽this system powerful is聽what鈥檚聽left out: the brain and spinal cord. By isolating motor neurons and muscle cells, the researchers could聽determine聽whether movement problems could arise without the central nervous system being involved.
To test this, the researchers聽paired聽healthy聽muscle cells聽with聽motor neurons聽that were聽created from stem cells聽and聽carried聽familial Alzheimer鈥檚 disease聽mutations.聽The聽findings suggest that Alzheimer鈥檚-related movement issues may begin in the network of nerves outside the brain and spinal cord rather than being caused solely by brain degeneration.
Why the聽Nerve-to-Muscle Connection Matters
The neuromuscular junction is the point where a nerve cell signals a muscle to contract, making movement possible.聽If that connection is damaged, the body may lose strength,聽coordination聽or endurance.
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.
鈥淵ou can鈥檛 move unless the motor circuit works,鈥� Hickman聽says. 鈥淲hen a doctor taps your knee to check your reflex, they鈥檙e testing that exact connection.鈥�
The Future of聽鈥楬uman-on-a-Chip鈥櫬燭echnology
The researchers believe their approach will become increasingly important as drug developers look for more聽accurate聽ways to study human disease.
Because the models use human cells and measure real biological聽function, they can reveal effects that may not appear in animal studies.
For Hickman, the work reflects聽30 years of research to聽better understand disease and help people.
鈥淭hese systems let us study disease in a way that鈥檚 closer to what actually happens in the human body, and that鈥檚 what we need to develop better treatments,鈥澛爃e says.
Research reported in this article was supported by the National Institutes of Health鈥檚 National Institute on Aging under award number R01AG077651 and R44AG071386. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
