Targeting the Post-Synaptic Proteome in Alzheimer Disease with Psychosis

ABSTRACT: Individuals with Alzheimer Disease with psychotic symptoms (AD+P) experience more rapid cognitive and functional decline, and have reduced indices of synaptic integrity, relative to those without psychosis (AD-P). We hypothesized the postsynaptic density (PSD) proteome is altered in AD+P relative to AD-P, and that this proteomic signature could be used to nominate novel pharmacotherapies. METHODS: Liquid-Chromatography/Mass Spectrometry analysis of PSDs from dorsolateral prefrontal cortex of AD+P, AD-P and cognitively normal elderly subjects. RESULTS: The PSD proteome signature of AD+P was characterized by lower levels of a network of kinases, proteins regulating Rho GTPases, and proteins regulating the actin cytoskeleton. Potential novel therapies identified included the C-C Motif Chemokine Receptor 5 inhibitor, maraviroc. DISCUSSION: AD+P is characterized by broad changes in the PSD proteome in prefrontal cortex. Further testing of potential therapies for their ability to reverse these changes and protect against psychotic-like behaviors in model systems is warranted.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Matthew MacDonald  

LAB HEAD: Matthew MacDonald

PROVIDER: PXD042026 | Pride | 2023-06-19

REPOSITORIES: Pride