title: Rationalising the role of Keratin 9 as a biomarker for Alzheimer's disease.
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.
authors.affiliation: Cell Biophysics Group, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Richens
authors.affiliation: Cell Biophysics Group, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Spencer
authors.affiliation: Cell Biophysics Group, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
authors.forename: Molly
authors.initials: M
authors.lastname: Butler
authors.affiliation: Cell Biophysics Group, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Cantlay
authors.affiliation: Cell Biophysics Group, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
authors.forename: Kelly-Ann
authors.initials: KA
authors.lastname: Vere
authors.affiliation: Department of Neurology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Nin
authors.initials: N
authors.lastname: Bajaj
authors.affiliation: School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.affiliation: Cell Biophysics Group, School of Life Sciences, University of Nottingham, University Park, Nottingham, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Shea
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D001812:Blood-Brain Barrier / Q000378:metabolism; D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053534:Keratin-9 / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps; D015398:Signal Transduction; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053534:Keratin-9; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D046988:Proteasome Endopeptidase Complex