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

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 mech...

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Main Authors: Richens, Joanna L., Spencer, Hannah L., Butler, Molly, Cantlay, Fiona, Vere, Kelly-Ann, Bajaj, Nin, Morgan, Kevin, O'Shea, Paul
Format: Article
Published: Nature Publishing Group 2016
Subjects:
Online Access:https://eprints.nottingham.ac.uk/32385/
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author Richens, Joanna L.
Spencer, Hannah L.
Butler, Molly
Cantlay, Fiona
Vere, Kelly-Ann
Bajaj, Nin
Morgan, Kevin
O'Shea, Paul
author_facet Richens, Joanna L.
Spencer, Hannah L.
Butler, Molly
Cantlay, Fiona
Vere, Kelly-Ann
Bajaj, Nin
Morgan, Kevin
O'Shea, Paul
author_sort Richens, Joanna L.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-323852020-05-04T17:42:01Z https://eprints.nottingham.ac.uk/32385/ 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 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. Nature Publishing Group 2016-03-14 Article PeerReviewed Richens, Joanna L., Spencer, Hannah L., Butler, Molly, Cantlay, Fiona, Vere, Kelly-Ann, Bajaj, Nin, 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 keratin 9 Alzheimer's disease http://www.nature.com/articles/srep22962 doi:10.1038/srep22962 doi:10.1038/srep22962
spellingShingle keratin 9
Alzheimer's disease
Richens, Joanna L.
Spencer, Hannah L.
Butler, Molly
Cantlay, Fiona
Vere, Kelly-Ann
Bajaj, Nin
Morgan, Kevin
O'Shea, Paul
Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease
title Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease
title_full Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease
title_fullStr Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease
title_full_unstemmed Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease
title_short Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease
title_sort rationalising the role of keratin 9 as a biomarker for alzheimer’s disease
topic keratin 9
Alzheimer's disease
url https://eprints.nottingham.ac.uk/32385/
https://eprints.nottingham.ac.uk/32385/
https://eprints.nottingham.ac.uk/32385/