MOTIVATION: In an effort to better understand the molecular drivers of synaptic 
and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed 
neuronal gene expression data from human AD brain tissue to identify master 
regulators of synaptic gene expression.
RESULTS: Master regulator analysis identifies ZCCHC17 as normally supporting the 
expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction 
in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is 
normally expressed in neurons and is reduced early in the course of AD 
pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of 
the majority of the predicted synaptic targets and that ZCCHC17 drives the 
expression of a similar gene network in humans and rats. These findings support 
a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an 
important early driver of lower synaptic gene expression in AD.
AVAILABILITY AND IMPLEMENTATION: Matlab and R scripts used in this paper are 
available at https://github.com/afteich/AD_ZCC.
CONTACT: aft25@cumc.columbia.edu.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics 
online.