F6 HUMAN HAIR FOLLICLE AND EPIDERMAL MELANOCYTES AS A PROXY CELL TYPE IN NEURODEGENERATION RESEARCH
Papageorgiou N, Carpenter E, Tobin DJ
Medical Biosciences, School of Life Sciences, University of Bradford, United Kingdom

Neurodegenerative disorders such as Alzheimer's disease (AD) are an increasing financial and social burden in ageing populations. AD pathology is associated with the deposition of amyloid beta peptides (Aß40 and Aß42) in the inter-neuronal space, leading to the formation of senile plaques. ?ß peptides are produced by cleavage of the amyloid precursor protein (APP) by ß- and ?-secretases. Recently, it has been shown that APP associates with transcription activator protein Fe65 resulting in its translocation to the nucleus, where it may be involved in gene modification. The post-mitotic nature of neurons limits the scope of neurodegeneration research to neuronal models. However, preliminary studies by others have suggested that other neural crest-derived cells may serve as a proxy for neurons in neurodegeneration research. This study aimed to assess whether human epidermal and hair follicle melanocytes are potential neuronal proxy candidates in the context of AD research. The expression of APP was assessed in epidermal and hair follicle melanocytes using antibodies raised against APP and melanocyte-specific glycoprotein 100 (gp100) in frozen sections of human haired scalp and in cultured human melanocytes in vitro. Expression of APP was noted in gp100-positive melanocytes distributed in the epidermis, hair bulb, and outer root sheath of scalp in all individuals tested. Furthermore, immunocytochemistry in cultured human melanocytes demonstrated cytoplasmic expression of Aß40 & Aß42, and also showed a nuclear expression of APP. Taken together, these data suggest similarity between the expression of APP and Aß peptides in human cutaneous melanocytes and neurons. Moreover, the nuclear expression of APP in melanocytes in situ and in vitro suggests its possible involvement with the translocation of the activator protein Fe65, further supporting the exploration of these highly accessible cutaneous melanocytes as a potential neuronal proxy in neurodegeneration research.