The Brain Injury Biomarker VLP-1 Is Increased in the Cerebrospinal Fluid of Alzheimer Disease Patients

Abstract

Abstract 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-β peptide (Aβ1–42), total Tau (tTau), and hyperphosphorylated Tau (pTau). methods: Using ELISA, we measured concentrations of Aβ1–42, 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 Aβ, 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 ε4/ε4 genotype [599 (240) ng/L] compared with ε3/ε4 [376 (127) ng/L] and ε3/ε3 [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 Aβ1–42 (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.