This review systematically summarizes the potential of the skin as a source of biomarkers for neurodegenerative diseases (NDDs), covering skin-related pathological mechanisms in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). It reviews the application of skin sampling techniques, such as immunohistochemistry, lipidomics, and volatile organic compound analysis, in early disease diagnosis, highlighting the bidirectional axis between the skin and the brain as well as shared molecular mechanisms. This provides new insights for non-invasive biomarker research in NDDs.
Literature Overview
This article, titled 'Exploring the skin as an open window onto neurodegenerative diseases' and published in the journal 'Translational Neurodegeneration', reviews and summarizes the potential of the skin as a source of biomarkers for neurodegenerative diseases (NDDs). The article details similarities between the skin and the central nervous system (CNS) in terms of developmental origin, gene expression, protein modifications, and cellular dysfunction, offering new strategies for early diagnosis and disease monitoring through skin sample analyses such as immunohistochemistry, lipidomics, and volatilomics.
Background Knowledge
Neurodegenerative diseases (NDDs) are age-related conditions characterized by protein misfolding, oxidative stress, mitochondrial and lysosomal dysfunction, and neuroinflammation, including AD, PD, and HD. These diseases often involve extensive neuronal damage even before clinical symptoms appear, making early diagnosis and intervention a key research focus. The skin, as a peripheral tissue, has emerged as a new window for studying NDDs due to its similarities in developmental and molecular features with brain tissue. Skin samples can be obtained through non-invasive methods (e.g., tape stripping, sebum collection) or minimally invasive techniques (e.g., skin biopsy) to detect changes such as pathological protein deposition, inflammatory cytokines, lipid metabolism, and oxidative stress. Recent studies have identified NDD-related proteins such as Aβ, α-synuclein, and tau in skin tissue, supporting the feasibility of using the skin as a peripheral source of biomarkers. Moreover, comorbid relationships between skin disorders, such as psoriasis, seborrheic dermatitis, rosacea, and melanoma, and NDDs also suggest that skin changes can reflect systemic inflammation and metabolic abnormalities, providing clues for early disease identification.
Research Methods and Experiments
This review integrates multiple studies analyzing pathological protein deposition, such as Aβ, α-synuclein (α-Syn), and phosphorylated tau (p-tau), in skin samples using techniques including immunohistochemistry, protein expression analysis, lipidomics, and volatilomics. It also explores the application of skin fibroblasts in in vitro models to simulate cellular dysfunction related to NDDs. Furthermore, the article summarizes potential associations between skin conditions, including skin inflammation, sebum secretion, and microbial community changes, and NDDs, emphasizing the skin as a non-invasive window to reflect changes in the CNS.
Key Conclusions and Perspectives
Research Significance and Prospects
The skin, as a peripheral tissue, can provide biomarkers for the early diagnosis of neurodegenerative diseases and enable non-invasive monitoring of disease progression. Future studies should standardize skin sampling and analysis methods to validate their diagnostic value in clinical settings. Additionally, understanding the bidirectional communication mechanisms between the skin and brain may identify new targets for neuroprotective interventions, promoting early detection and precision medicine for NDDs.
Conclusion
With the increasing global aging population, early diagnosis and intervention of neurodegenerative diseases have become major public health challenges. The skin, due to its shared developmental and molecular features with the central nervous system, has emerged as a new window for studying NDDs. Skin sample analysis can detect pathological protein deposition, inflammatory cytokines, oxidative stress, and lipid metabolism abnormalities, providing non-invasive tools for disease monitoring and biomarker discovery. This review highlights the research advances in skin sampling techniques for AD, PD, and HD, and proposes the potential value of the skin as a peripheral tissue in disease model validation, mechanistic studies, and personalized therapy. Future research needs to further optimize skin sampling and analysis protocols to facilitate their broader application in clinical practice.
