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

Sci Rep. 2016 Mar 14:6:22962. doi: 10.1038/srep22962.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Apolipoproteins E / metabolism
  • Biomarkers / analysis*
  • Biomarkers / blood
  • Blood-Brain Barrier / metabolism
  • Cohort Studies
  • Computational Biology / methods
  • Female
  • Humans
  • Immunoassay / methods
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratin-9 / analysis*
  • Keratin-9 / metabolism
  • Keratin-9 / physiology
  • Male
  • Peptide Fragments / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Binding
  • Protein Interaction Maps
  • Signal Transduction*
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Biomarkers
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Keratin-9
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Proteasome Endopeptidase Complex