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Skin-Based Biomarkers to Enable Early Diagnosis of Amyotrophic Lateral Sclerosis

By LabMedica International staff writers
Posted on 15 Aug 2025

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that damages motor neurons in the brain and spinal cord, causing muscle weakness, paralysis, and death within three to five years of symptom onset. More...

While some cases are inherited, most occur sporadically. Early diagnosis is crucial for better outcomes, but remains difficult due to inconclusive early-stage tests and limitations of current diagnostic tools. Now, skin-based biomarkers could enable earlier diagnosis of ALS.

Researchers from Chifeng Municipal Hospital (Chifeng, China) are exploring the skin as a potential early diagnostic source for ALS. The skin shares an embryonic origin with the central nervous system, meaning molecular and cellular changes in the nervous system may be mirrored in skin tissue. Similar approaches have detected abnormal protein deposits in Parkinson’s disease skin before neurological symptoms emerge, suggesting this pathway could be valuable in ALS as well.

Studies in ALS patients and at-risk individuals have revealed structural skin abnormalities such as disorganized collagen fibers, thickened blood vessel walls, and subtle changes in people with ALS-related genetic mutations before symptoms appear. Microscopic analysis shows vascular alterations, including “onion-skin” formations and reduced angiogenin levels, while nerve fiber loss has been linked to altered sweating, temperature sensation, and neuropathic pain.

On a molecular level, skin cells show abnormal aggregation of ALS-linked proteins such as SOD1, TDP-43, and FUS, indicating that protein misfolding extends beyond neurons. Damaged mitochondria in skin cells exhibit reduced energy production and increased oxidative stress, mirroring central nervous system pathology. Inflammatory changes, including higher pro-inflammatory cytokines and lower regulatory immune cells, further suggest systemic immune involvement.

Additional findings, including increased MMP-9 and decreased galectin-1, point to pathways connecting skin pathology directly to motor neuron degeneration. These results, published in Biomolecules and Biomedicine, indicate that skin could serve as a minimally invasive “window” into ALS biology. Potential diagnostic approaches include small biopsies, nerve fiber density measurements, and targeted molecular assays.

If validated in larger and more diverse studies, skin-based biomarkers could shorten diagnostic delays, improve patient management, and provide new insights into ALS mechanisms. This could help guide the development of targeted treatments and potentially replace more invasive testing methods. Researchers have emphasized the need for expanded trials before clinical adoption.


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