β-Amyloid 42/40 ratio and kalirin expression in Alzheimer disease with psychosis

Patrick S. Murray, Caitlin M. Kirkwood, Megan C. Gray, Milos D. Ikonomovic, William R. Paljug, Eric E. Abrahamson, Ruth A. Henteleff, Ronald L. Hamilton, Julia K. Kofler, William E. Klunk, Oscar L. Lopez, Peter Penzes, Robert A. Sweet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Psychosis in Alzheimer disease differentiates a subgroup with more rapid decline, is heritable, and aggregates within families, suggesting a distinct neurobiology. Evidence indicates that greater impairments of cerebral cortical synapses, particularly in dorsolateral prefrontal cortex, may contribute to the pathogenesis of psychosis in Alzheimer disease (AD) phenotype. Soluble β-amyloid induces loss of dendritic spine synapses through impairment of long-term potentiation. In contrast, the Rho guanine nucleotide exchange factor (GEF) kalirin is an essential mediator of spine maintenance and growth in cerebral cortex. We therefore hypothesized that psychosis in AD would be associated with increased soluble β-amyloid and reduced expression of kalirin in the cortex. We tested this hypothesis in postmortem cortical gray matter extracts from 52 AD subjects with and without psychosis. In subjects with psychosis, the β-amyloid1-42/β-amyloid1-40 ratio was increased, due primarily to reduced soluble β-amyloid1-40, and kalirin-7, -9, and -12 were reduced. These findings suggest that increased cortical β-amyloid1-42/β-amyloid1-40 ratio and decreased kalirin expression may both contribute to the pathogenesis of psychosis in AD.

Original languageEnglish (US)
Pages (from-to)2807-2816
Number of pages10
JournalNeurobiology of Aging
Volume33
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • Alzheimer disease
  • Kalirin
  • Psychosis
  • β-amyloid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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