Visinin‐like protein‐1: Diagnostic and prognostic biomarker in Alzheimer disease

Abstract

Objective There is a growing need to identify cerebrospinal fluid (CSF) markers that can detect Alzheimer’s disease (AD) pathology in cognitively normal individuals since 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. We here investigate CSF VILIP-1 and VILIP-1/amyloid-β42 (Aβ42) ratio as diagnostic and prognostic markers in early AD. Methods 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. 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/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. Interpretation 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.

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

“…AD risk groups within the MCI groups of patients were defined by the levels of five CSF AD biomarkers (Aβ 1-42 , t-tau, p-tau 181 ,p-tau 199 , and ptau 231 ). We tested VILIP-1 effectiveness in early detection of AD in MCI patients, and confirmed previous observations that VILIP-1 is a useful biomarker in early AD diagnosis [12,17,[27][28][29][30]]. Additionally, we tested VILIP-1 potential in differentiating AD from other primary causes of dementia, and its ability in predicting disease progression.…”

“…Surprisingly, there was no significant difference in VILIP-1 levels between patients with mild and moderate AD. Other authors however reported that VILIP-1 levels and VILIP-1/Aβ 1-42 ratio predict cognitive decline in cognitively healthy individuals and AD patients [27,28]. Both parameters predicted conversion of CDR 0 HC group to CDR 0.5 or higher [27].…”

“…Also, recent genome-wide association studies (GWAS) showed an association of polymorphisms in VILIP-1 and VILIP-3 genes with the occurrence of AD [25,26]. Altogether, these factors may contribute to neuronal cell death and to the increase of VILIP-1 in CSF of AD patients [12,17,[27][28][29][30]. VILIP-1 levels were also increased in plasma of AD patients [27].…”

“…Altogether, these factors may contribute to neuronal cell death and to the increase of VILIP-1 in CSF of AD patients [12,17,[27][28][29][30]. VILIP-1 levels were also increased in plasma of AD patients [27]. Recent studies reported the diagnostic potential of VILIP-1 in AD detection at early stages and in monitoring of disease progression [17,28].…”

Cerebrospinal fluid biomarkers of Alzheimer’s disease

“…The ratio of YKL-40 to Aβ42 predicts cognitive impairment as well as the best CSF biomarkers (Aβ42, t-tau, and p-tau) [83] , suggesting potential as a biomarker for preclinical AD. dementias, and that CSF VILIP-1/Aβ42 predicts cognitive impairment as well as tau/Aβ42 and p-tau181/Aβ42 [84,85] . …”