title: The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients.
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-beta peptide (Abeta(1-42)), total Tau (tTau), and hyperphosphorylated Tau (pTau).
  
  
  METHODS
  Using ELISA, we measured concentrations of Abeta(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 Abeta, 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 epsilon4/epsilon4 genotype [599 (240) ng/L] compared with epsilon3/epsilon4 [376 (127) ng/L] and epsilon3/epsilon3 [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 Abeta(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.
authors.affiliation: Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Niels
authors.initials: N
authors.lastname: Andreasen
authors.forename: Omar
authors.initials: O
authors.lastname: Laterza
authors.forename: Vijay
authors.initials: V
authors.lastname: Modur
authors.forename: Jitka
authors.initials: J
authors.lastname: Olander
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Matt
authors.initials: M
authors.lastname: Ohlendorf
authors.forename: Jack H
authors.initials: JH
authors.lastname: Ladenson
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D051596:Neurocalcin / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D051596:Neurocalcin; C496688:VSNL1 protein, human