Brain Biomarkers: Follow-Up of RNA Expression Discovery Approach: CSF Assays for Neurogranin, SNAP-25, and VILIP-1

Abstract

Here, we describe our methods for identifying biomarkers of neurological disease that have the potential to evaluate patients with probable Alzheimer’s disease (AD) and efficacy of novel therapeutics. We report a follow-up to our RNA expression discovery approach in mice to identify potential brain biomarkers. The gene expression approach identified 26 genes as having reasonable abundance and specificity and with human homologs known at the time. This chapter describes our follow-up in developing and evaluating the assays for the proteins expressed by these genes. We then present validated working assays for three analytes: VILIP-1 (visinin-like protein 1), a robust marker of neurodegeneration; synaptosomal-associated protein-25 (SNAP-25) and two different assays for neurogranin (Ng), as biomarkers of synaptic pathology, that we have utilized for studying AD, and which have demonstrated diagnostic utility.