Synaptic Proteome Compensation and Resilience to Psychosis in Alzheimer's Disease

The American Journal of Psychiatry
Josh M KrivinkoJulia Kofler

Abstract

The presence of psychosis in Alzheimer's disease denotes a phenotype with more rapid cognitive deterioration than in Alzheimer's disease without psychosis. Discovery of novel pharmacotherapies that engage therapeutic targets for prevention or treatment of Alzheimer's disease with psychosis would benefit from identifying the neurobiology of resilience to psychosis in Alzheimer's disease. The primary objective of this study was to determine whether alterations in the synaptic proteome were associated with resilience to psychotic symptoms in Alzheimer's disease and, if present, were independent of neuropathologic burden. Quantitative immunohistochemistry was used to measure multiple neuropathologies in dorsolateral prefrontal cortex from subjects with early and middle-stage Alzheimer's disease who differed in psychosis status. Synaptic proteins were quantified by liquid chromatography-mass spectrometry in gray matter homogenates from these subjects and from neuropathologically unaffected subjects. The synaptic proteome was similarly evaluated in cortical gray matter homogenate and in postsynaptic density fractions from an APPswe/PSEN1dE9 mouse model of amyloidosis with germline reduction in Kalrn, which has been shown to confer re...Continue Reading

Citations

Dec 7, 2018·Current Opinion in Psychiatry·Wael K KaramehCorinne E Fischer
Aug 1, 2020·Annals of Clinical and Translational Neurology·Oscar L LopezWilliam E Klunk
Oct 14, 2020·Current Neurology and Neuroscience Reports·Clive BallardRobert A Sweet
Feb 3, 2020·Neurobiology of Aging·Ehsan PishvaKatie Lunnon
Feb 6, 2021·Journal of Neurochemistry·Callista B Harper, Karen J Smillie
Jun 12, 2021·Molecular Psychiatry·Mary Ann A DeMichele-SweetRobert A Sweet

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