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

Richens, Joanna L.; Spencer, Hannah L.; Butler, Molly; Cantlay, Fiona; Vere, Kelly-Ann; Bajaj, Nin; Morgan, Kevin; O'Shea, Paul

Authors

Joanna L. Richens

Hannah L. Spencer

Molly Butler

Fiona Cantlay

Kelly-Ann Vere

Nin Bajaj

KEVIN MORGAN kevin.morgan@nottingham.ac.uk
Professor of Human Genomics and Molecular Genetics

Paul O'Shea



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.

Journal Article Type Article
Publication Date Mar 14, 2016
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 6
Issue 22962
APA6 Citation Richens, J. L., Spencer, H. L., Butler, M., Cantlay, F., Vere, K., Bajaj, N., …O'Shea, P. (2016). Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease. Scientific Reports, 6(22962), doi:10.1038/srep22962
DOI https://doi.org/10.1038/srep22962
Keywords keratin 9, Alzheimer's disease
Publisher URL http://www.nature.com/articles/srep22962
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0



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