Neurogranin and VILIP-1 as Molecular Indicators of Neurodegeneration in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Neurogranin (Ng) and visinin-like protein 1 (VILIP-1) are promising candidates for Alzheimer’s Disease (AD) biomarkers closely related to synaptic and neuronal degeneration. Both proteins are involved in calcium-mediated pathways. The meta-analysis was performed in random effects based on the ratio of means (RoM) with calculated pooled effect size. The diagnostic utility of these proteins was examined in cerebrospinal fluid (CSF) of patients in different stages of AD compared to control (CTRL). Ng concentration was also checked in various groups with positive (+) and negative (-) amyloid beta (Aβ). Ng highest levels of RoM were observed in the AD (n = 1894) compared to CTRL (n = 2051) group (RoM: 1.62). Similarly, the VILIP-1 highest values of RoM were detected in the AD (n = 706) compared to CTRL (n = 862) group (RoM: 1.34). Concentrations of both proteins increased in more advanced stages of AD. However, Ng seems to be an earlier biomarker for the assessment of cognitive impairment. Ng appears to be related with amyloid beta, and the highest levels of Ng in CSF was observed in the group with pathological Aβ+ status. Our meta-analysis confirms that Ng and VILIP-1 can be useful CSF biomarkers in differential diagnosis and monitoring progression of cognitive decline. Although, an additional advantage of the protein concentration Ng is the possibility of using it to predict the risk of developing cognitive impairment in normal controls with pathological levels of Aβ1-42. Analyses in larger cohorts are needed, particularly concerning Aβ status.