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


Maximus Peto’s Commentary

This group found alpha-synuclein, tau, and Abeta 1-34 in skin cells; if I’m reading the abstract correctly, alpha-synuclein was in the nucleus of some cells.


Neurodegenerative Disease-Related Proteins within the Epidermal Layer of the Human Skin.
J Alzheimers Dis. 2019;69(2):463-478.
Akerman SC, Hossain S, Shobo A, Zhong Y, Jourdain R, Hancock MA, George K, Breton L, Multhaup G
DOI: 10.3233/JAD-181191
PubMed publication date (edat): 4/23/2019

Abstract

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 α-synuclein was detected throughout the epidermal layer of the auricular samples (IHC and MALDI-MSI), tau and Aβ34 were also localized to the epidermal layer (IHC). In addition to Aβ peptides of varying length (e.g., Aβ40, Aβ42, Aβ34), we also were able to detect inflammatory markers within the same sample sets (e.g., thymosin β-4, psoriasin). While previous literature has described α-synuclein in the nucleus of neurons (e.g., Parkinson’s disease), our current detection of α-synuclein in the nucleus of skin cells is novel. Imaging of α-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 Aβ34 in human skin suggests that, just like in the brain, it may represent a stable intermediate of the Aβ40 and Aβ42 degradation pathway.

PMID: 31006686
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Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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