Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

Richens, Joanna L. and Spencer, Hannah L. and Butler, Molly and Cantlay, Fiona and Vere, Kelly-Ann and Bajaj, Nin and Morgan, Kevin and O'Shea, Paul (2016) Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease. Scientific Reports, 6 (22962). pp. 1-12. ISSN 2045-2322

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Abstract

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression.

Item Type: Article
Keywords: keratin 9, Alzheimer's disease
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Molecular Medical Sciences > Human Genetics Research Group
Identification Number: https://doi.org/10.1038/srep22962
Depositing User: Morgan, Kevin
Date Deposited: 18 Mar 2016 13:56
Last Modified: 14 Sep 2016 07:15
URI: http://eprints.nottingham.ac.uk/id/eprint/32385

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