Visinin-like Protein-1: Diagnostic and Prognostic Biomarker in Alzheimer Disease

Objective: 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 similar to 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-beta 42 (A beta 42) ratio as diagnostic and prognostic markers in early AD. Methods: We assessed CSF levels of VILIP-1, tau, phosphorylated-tau181 (p-tau181), and A beta 42 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. Results: 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/A beta 42 predicted future cognitive impairment in CNC over the follow-up period. Importantly, CSF VILIP-1/A beta 42 predicted future cognitive impairment at least as well as tau/A beta 42 and p-tau181/A beta 42. Interpretation: These findings suggest that CSF VILIP-1 and VILIP-1/A beta 42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/A beta 42, respectively. ANN NEUROL 2011;70:274-285