Received on February 5, 2008
Accepted on July 2, 2008

Proteomics and Protein Markers

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

¹ The Hope Center for Neurological Disorders and the Department of Neurology, Washington University School of Medicine, St. Louis, MO
² Clinical Neurochemistry Laboratory, Department of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden
³ Memory Clinic, Department of Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden
⁴ Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
⁵ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO

^* To whom correspondence should be addressed. E-mail: ladenson{at}wustl.edu.

BACKGROUND: Definitive diagnosis of Alzheimer's 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- peptide (A_1–42), total Tau (tTau), and hyperphosphorylated Tau (pTau).

METHODS: Using ELISA, we measured concentrations of A_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, 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 4/4 genotype [599 (240) ng/L] compared with 3/e4 [376 (127) ng/L] and 3/3 [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_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.