Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid

Abstract

In the search for biomarkers of synapse loss associated with Alzheimer's disease (AD), we used shotgun proteomics to identify a panel of 9 synaptic proteins detectable in human cerebrospinal fluid (CSF). Expression at the human synapse was verified using super resolution microscopy. Using SRM, we monitored the panel in CSF from 3 independent clinical cohorts. We report 6 synaptic biomarkers that demonstrate changes in preclinical AD prior to markers of neurodegeneration, which could have clinical value for assessing disease progression.