title: Dkk-3 is elevated in CSF and plasma of Alzheimer's disease patients.
abstract: Biomarkers in CSF can offer improved diagnostic accuracy for Alzheimer's disease (AD). The present study investigated whether the glycoprotein and putative tumor suppressor Dickkopf homolog 3 (Dkk-3) is secreted into CSF and evaluated its applicability as a diagnostic marker for AD. Using our highly specific immunoenzymometric assay, Dkk-3 levels were measured in plasma and/or CSF of patients suffering from depression, mild cognitive impairment (MCI), or AD and compared with healthy subjects. Dkk-3 identity was verified by western blot and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)/MS. High concentrations of Dkk-3 were detected in CSF compared with plasma (28.2 +/- 1.3 vs. 1.22 +/- 0.04 nmol/L, respectively). Consistently Dkk-3 expression was demonstrated in neurons of the cortex and epithelial cells of the choroid plexus, the major source of CSF. Significantly increased Dkk-3 levels in plasma and CSF were observed for AD patients compared with healthy subjects but not patients suffering from MCI or depression. In summary, our data indicate that elevated Dkk-3 levels are specifically associated with AD and might serve as a potential non-invasive AD biomarker in plasma.
authors.affiliation: Institute for Biomedical Aging Research, Innsbruck, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zenzmaier
authors.forename: Josef
authors.initials: J
authors.lastname: Marksteiner
authors.forename: Andreas
authors.initials: A
authors.lastname: Kiefer
authors.forename: Peter
authors.initials: P
authors.lastname: Berger
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology*; D018925:Chemokines; D003072:Cognition Disorders / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003863:Depression / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins