Journal
CLINICAL CHEMISTRY
Volume 54, Issue 10, Pages 1617-1623Publisher
AMER ASSOC CLINICAL CHEMISTRY
DOI: 10.1373/clinchem.2008.104497
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Funding
- NINDS NIH HHS [R01 NS048283-04, R01 NS048283, P01 NS032636-139001, P01 NS032636, R01 NS048283-03] Funding Source: Medline
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BACKGROUND: Definitive diagnosis of Alzheimer disease (AD) can be made only by histopathological examination of brain tissue, prompting the search for premortem disease biomarkers. We sought to determine if the novel brain injury biomarker, visinin-like protein 1 (VLP-1), is altered in the CSF of AD patients compared with controls, and to compare its values to the other well-studied CSF biomarkers 42-amino acid amyloid-beta peptide (A beta(1-42)) total Tau (tTau), and hyperphosphorylated Tau (pTau). METHODS: Using ELISA, we measured concentrations of A beta(1-42) tTau, pTau, and VLP-1 in CSF samples from 33 AD patients and 24 controls. We compared the diagnostic performance of these biomarkers using ROC curves. RESULTS: CSF VLP-1 concentrations were significantly higher in AD patients [median (interquartile range) 365 (166) ng/L] compared with controls [244 (142.5) ng/L]. Although the diagnostic performance of VLP-1 alone was comparable to that of A beta, tTau, or pTau alone, the combination of the 4 biomarkers demonstrated better performance than each individually. VLP-1 concentrations were higher in AD subjects with APOE epsilon 4/epsilon 4 genotype [599 (240) ng/L] compared with epsilon 3/epsilon 4 [376 (127) ng/L] and 010 [280 (115.5) ng/L] genotypes. Furthermore, VLP-1 values demonstrated a high degree of correlation with pTau (r = 0.809) and tTau (r = 0.635) but not A beta(1-42) (r = -0.233). VLP-1 was the only biomarker that correlated with MMSE score (r = -0.384, P = 0.030). CONCLUSIONS: These results suggest that neuronal injury markers such as VLP-1 may have utility as biomarkers for AD. (c) 2008 American Association for Clinical Chemistry.
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