Dkk-3 is elevated in CSF and plasma of Alzheimer's disease patients

作者：Zenzmaier Christoph; Marksteiner Josef; Kiefer Andreas; Berger Peter^*; Humpel Christian

来源：Journal of Neurochemistry, 2009, 110(2): 653-661.

DOI：10.1111/j.1471-4159.2009.06158.x

• beta-amyloid (1-42)
• Alzheimer's disease
• CSF
• Dickkopf-3
• p-tau-181
• tau

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.

• 出版日期2009-7