Neurodegenerative Disease-Related Proteins within the Epidermal Layer of the Human Skin

There is increasing evidence suggesting that amyloidogenic proteins might form deposits in non-neuronal tissues in neurodegenerative disorders such as Alzheimer's or Parkinson's diseases. However, the detection of these aggregation-prone proteins within the human skin has been controversial. Using immunohistochemistry (IHC) and mass spectrometry tissue imaging (MALDI-MSI), fresh frozen human skin samples were analyzed for the expression and localization of neurodegenerative disease-related proteins. While alpha-synuclein was detected throughout the epidermal layer of the auricular samples (IHC and MALDI-MSI), tau and A beta(34) were also localized to the epidermal layer (IHC). In addition to A beta peptides of varying length (e.g., A beta(40), A beta(42), A beta(34)), we also were able to detect inflammatory markers within the same sample sets (e.g., thymosin beta-4, psoriasin). While previous literature has described alpha-synuclein in the nucleus of neurons (e.g., Parkinson's disease), our current detection of alpha-synuclein in the nucleus of skin cells is novel. Imaging of alpha-synuclein or tau revealed that their presence was similar between the young and old samples in our present study. Future work may reveal differences relevant for diagnosis between these proteins at the molecular level (e.g., age-dependent post-translational modifications). Our novel detection of A beta(34) in human skin suggests that, just like in the brain, it may represent a stable intermediate of the A beta(40) and A beta(42 )degradation pathway.