Psychosis in Alzheimer's Disease Is Associated With Increased Excitatory Neuron Vulnerability and Post-transcriptional Mechanisms Altering Synaptic Protein Levels.

Alzheimer's disease with psychosis (AD+P) is a heritable phenotypic variant of the disease which is associated with more rapid cognitive deterioration compared to Alzheimer's disease without psychosis (AD-P). Cognitive decline in AD correlates with synapse loss, and our previous studies suggest that those with AD+P have a differentially affected synaptic proteome relative to those with AD-P. In this study, we utilized RNA-sequencing of dorsolateral prefrontal cortex (DLPFC) in a cohort of 80 AD cases to evaluate novel transcriptomic signatures that may confer risk of psychosis in AD.