Skin Biomarkers as a Promising Tool for Early Diagnosis of Amyotrophic Lateral Sclerosis (ALS)

Recent research suggests that skin-based biomarkers could revolutionize the early diagnosis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons in the brain and spinal cord. ALS typically leads to muscle weakness, paralysis, and often results in death within three to five years of symptom onset. Although most cases are sporadic, approximately 10% are inherited due to specific genetic mutations.

Currently, diagnosing ALS remains challenging. Traditional methods, such as neurological exams, electromyography, and brain imaging, can be inconclusive during early stages, causing significant delays—sometimes over a year—in accurate diagnosis. Blood tests offer limited specificity, and cerebrospinal fluid sampling is invasive. As a result, there is a pressing need for novel, minimally invasive diagnostic tools.

Emerging evidence highlights the potential of skin tissue analysis as an early biomarker source. Since the skin shares an embryonic origin with the central nervous system, cellular and molecular alterations present in the nervous system may also appear in skin tissues. Notably, studies in ALS have identified structural abnormalities in the skin, including disorganized collagen fibers, thickened blood vessel walls, and subtle cellular changes preempting symptom development in genetically predisposed individuals.

Further investigation has revealed that nerve fibers responsible for sensation and autonomic functions are reduced in density within the skin of ALS patients. These reductions can lead to altered sweating, temperature sensations, and neuropathic pain. Microscopic examinations have also shown vascular changes that resemble the layered 'onion-skin' formations seen in nerve tissues, alongside decreased levels of angiogenin, a protein vital for blood vessel health.

Remarkably, skin cells from ALS patients show abnormal protein aggregates, such as SOD1, TDP-43, and FUS, which are strongly associated with the disease’s pathology. Additionally, mitochondria in skin cells display signs of damage, reduced energy production, and increased oxidative stress, reflecting similar changes observed in neurons. Inflammatory processes are also evident, with elevated pro-inflammatory cytokines and diminished regulatory immune cells, indicating systemic immune dysregulation within the disease framework.

These discoveries, published in Biomolecules and Biomedicine, suggest that the skin could serve as a non-invasive 'window' into ALS at its early stages. Techniques such as small biopsies, nerve fiber density assessments, and molecular assays could potentially supplement or replace more invasive diagnostic procedures, enabling earlier detection and improved disease management.

However, researchers emphasize the need for larger and more diverse studies to validate these findings before they are integrated into clinical practice. If confirmed, skin-based biomarkers could significantly reduce diagnostic delays, enhance patient care, and unlock new understanding of ALS mechanisms, ultimately fostering the development of more effective therapies.

Source: https://medicalxpress.com/news/2025-08-skin-based-biomarkers-earlier-diagnosis.html