Dkk‐3 is elevated in CSF and plasma of Alzheimer’s disease patients

• Published in: Journal of neurochemistry Vol. 110; no. 2; pp. 653 - 661
• Main Authors: Zenzmaier, Christoph, Marksteiner, Josef, Kiefer, Andreas, Berger, Peter, Humpel, Christian
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2009; Wiley-Blackwell
• Subjects: Adaptor Proteins, Signal Transducing; Adult; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amino Acid Sequence; Biological and medical sciences; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; biosynthesis; blood; Brain; Brain - metabolism; Brain - pathology; Cellular Senescence; Cellular Senescence - physiology; cerebrospinal fluid; Chemokines; Cognition Disorders; Cognition Disorders - blood; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - diagnosis; CSF; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Depression; Depression - blood; Depression - cerebrospinal fluid; Depression - diagnosis; diagnosis; Dickkopf‐3; Humans; Intercellular Signaling Peptides and Proteins; Intercellular Signaling Peptides and Proteins - biosynthesis; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - cerebrospinal fluid; Intercellular Signaling Peptides and Proteins - isolation & purification; isolation & purification; Male; Medical diagnosis; Medical sciences; metabolism; Middle Aged; Molecular biology; Molecular Sequence Data; Neurology; Neurosciences; Organic mental disorders. Neuropsychology; pathology; physiology; Plasma; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; p‐tau‐181; tau; β‐amyloid (1–42); Mood disorder; Choroid plexus; Ependymal organ; β-amyloid (1―42); Nervous system diseases; Cognitive disorder; Dickkopf-3; Alzheimer disease; Central nervous system; Glycoprotein; Depression; tau; p-tau-181; Cerebral disorder; Accuracy; Neuron; Central nervous system disease; CSF; Epithelial cell; Tumor; Degenerative disease; mild cognitive impairment; Mass spectrometry; Alzheimer's disease
• DOI: 10.1111/j.1471-4159.2009.06158.x
• ISSN: 0022-3042; 1471-4159

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.