Skin pathology in ALS: Diagnostic implications and biomarker potential

Ying  Gao; Yanchao  Lu; Ranran  Chen; Shumin  Zhao; Jialing  Liu; Sutian  Zhang; Xue  Bai; Jingjing  Zhang

doi:10.17305/bb.2025.12100

Authors

Ying Gao Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China https://orcid.org/0009-0006-7573-1619
Yanchao Lu Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China https://orcid.org/0009-0000-0426-2559
Ranran Chen Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China
Shumin Zhao Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China
Jialing Liu Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China https://orcid.org/0009-0006-2603-813X
Sutian Zhang Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China https://orcid.org/0009-0007-2310-9999
Xue Bai Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China
Jingjing Zhang Department of Neurology, Medical Research Center, Chifeng Municipal Hospital, Chifeng, China; Chifeng Clinical Medical College of Inner Mongolia Medical University, Chifeng, China https://orcid.org/0000-0002-4836-9304

DOI:

https://doi.org/10.17305/bb.2025.12100

Keywords:

Amyotrophic lateral sclerosis, ALS, skin, biomarkers, diagnosis, protein aggregation

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons in the spinal cord and brain, resulting in motor deficits and muscle atrophy. Approximately 5–10% of ALS patients are familial (fALS), while the rest are sporadic (sALS). Currently, early diagnosis of ALS cannot be achieved based on clinical manifestations and electromyography due to the lack of effective and easily available biomarkers. The skin and central nervous system (CNS) share the same embryonic origin. Several skin biomarkers have been found in many neurodegenerative diseases, such as abnormal deposition of pathological α-synuclein (α-Syn) in Parkinson's disease. Thus, molecular changes in the skin associated with ALS-specific pathological events could readily be detected and become biomarkers for ALS through skin testing. Here, we summarize the literature on pathological changes in the skin of ALS patients and animal models, including structural abnormalities of the skin, reduced density of skin nerve fibers, abnormal protein aggregation, altered mitochondrial morphology and function, and dysregulation of skin inflammation, which may be useful for early diagnosis and monitoring of ALS progression.