Predictive Value of Cerebrospinal Fluid Visinin-Like Protein-1 Levels for Alzheimer's Disease Early Detection and Differential Diagnosis in Patients with Mild Cognitive Impairment

J Alzheimers Dis. 2016;50(3):765-78. doi: 10.3233/JAD-150705.


Visinin-like protein 1 (VILIP-1) recently emerged as a potential biomarker of Alzheimer's disease (AD). This neuronal calcium sensor protein previously used as a marker of acute ischemic stroke is elevated in the cerebrospinal fluid (CSF) of AD patients. The goal of this study was to assess CSF VILIP-1 potential in early AD diagnosis and in differentiating mild cognitive impairment (MCI) patients with and without risk of AD. Additionally, we tested VILIP-1 ability to differentiate AD from other primary causes of dementia, and predict the progression of AD-related cognitive decline. VILIP-1 levels were compared with five CSF AD biomarkers (t-tau, Aβ1-42, p-tau181, p-tau199, and p-tau231). VILIP-1 successfully differentiated two MCI patient groups characterized by absence or presence of pathological levels of these CSF biomarkers, except for t-tau. VILIP-1/Aβ(1-42) and VILIP-1/p-tau181 ratios also differentiated MCI patients with pathological CSF biomarker levels. However, there was no difference in VILIP-1 levels between AD and MCI patients. VILIP-1/Aβ(1-42) and VILIP-1/p-tau231 ratios reached high sensitivities (above 70%) and very high specificities (above 85%) in differentiating AD patients from HC. Additionally, VILIP-1 differentiated AD from patients with Lewy body disease with 77.1% sensitivity and 100% specificity. VILIP-1 potential as a prognostic biomarker of cognitive decline in AD was also proved since VILIP-1/t-tau, VILIP-1/p-tau181, and VILIP-1/p-tau231 ratios correlated with MMSE scores. These data indicate that VILIP-1 alone or in combination with other AD CSF biomarkers represent a valuable marker for the early diagnosis of AD, recognition of MCI patients at higher risk to develop dementia, and in differentiating AD from LBD.

Keywords: Alzheimer’s disease; biomarker; cerebrospinal fluid; dementia; early diagnosis; mild cognitive impairment; visinin-like protein 1 (VILIP-1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis*
  • Diagnosis, Differential*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Neurocalcin / cerebrospinal fluid*
  • Peptide Fragments / cerebrospinal fluid
  • Predictive Value of Tests
  • ROC Curve
  • Statistics as Topic
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Neurocalcin
  • Peptide Fragments
  • VSNL1 protein, human
  • amyloid beta-protein (1-42)
  • tau Proteins