Visinin-like protein-1: Diagnostic and prognostic biomarker in Alzheimer disease
Article first published online: 5 AUG 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 2, pages 274–285, August 2011
How to Cite
Tarawneh, R., D'Angelo, G., Macy, E., Xiong, C., Carter, D., Cairns, N. J., Fagan, A. M., Head, D., Mintun, M. A., Ladenson, J. H., Lee, J.-M., Morris, J. C. and Holtzman, D. M. (2011), Visinin-like protein-1: Diagnostic and prognostic biomarker in Alzheimer disease. Ann Neurol., 70: 274–285. doi: 10.1002/ana.22448
- Issue published online: 5 AUG 2011
- Article first published online: 5 AUG 2011
- Accepted manuscript online: 7 APR 2011 02:15PM EST
- Manuscript Accepted: 1 APR 2011
- Manuscript Revised: 21 MAR 2011
- Manuscript Received: 17 JAN 2011
- National Institutes of Health. Grant Numbers: P50-AG05681, P01-AG03991, P01-AG26276, P30-NS057105, R01-NS67905, P50-NS55977
There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer's disease (AD) pathology in cognitively normal individuals because it is in this population that disease-modifying therapies may have the greatest chance of success. While AD pathology is estimated to begin ∼10–15 years prior to the onset of cognitive decline, substantial neuronal loss is present by the time the earliest signs of cognitive impairment appear. Visinin-like protein-1 (VILIP-1) has demonstrated potential utility as a marker of neuronal injury. Here we investigate CSF VILIP-1 and VILIP-1/amyloid-β42 (Aβ42) ratio as diagnostic and prognostic markers in early AD.
We assessed CSF levels of VILIP-1, tau, phosphorylated-tau181 (p-tau181), and Aβ42 in cognitively normal controls (CNC) (n = 211), individuals with early symptomatic AD (n = 98), and individuals with other dementias (n = 19). Structural magnetic resonance imaging (n = 192) and amyloid imaging with Pittsburgh Compound-B (n = 156) were obtained in subsets of this cohort. Among the CNC cohort, 164 individuals had follow-up annual cognitive assessments for 2–3 years.
CSF VILIP-1 levels differentiated individuals with AD from CNC and individuals with other dementias. CSF VILIP-1 levels correlated with CSF tau, p-tau181, and brain volumes in AD. VILIP-1 and VILIP-1/Aβ42 predicted future cognitive impairment in CNC over the follow-up period. Importantly, CSF VILIP-1/Aβ42 predicted future cognitive impairment at least as well as tau/Aβ42 and p-tau181/Aβ42.
These findings suggest that CSF VILIP-1 and VILIP-1/Aβ42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/Aβ42, respectively. ANN NEUROL 2011;