title: β-Amyloid 42/40 ratio and kalirin expression in Alzheimer disease with psychosis.
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-amyloid(1-42)/β-amyloid(1-40) ratio was increased, due primarily to reduced soluble β-amyloid(1-40), and kalirin-7, -9, and -12 were reduced. These findings suggest that increased cortical β-amyloid(1-42)/β-amyloid(1-40) ratio and decreased kalirin expression may both contribute to the pathogenesis of psychosis in AD.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Murray
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Kirkwood
authors.forename: Megan C
authors.initials: MC
authors.lastname: Gray
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.forename: William R
authors.initials: WR
authors.lastname: Paljug
authors.forename: Eric E
authors.initials: EE
authors.lastname: Abrahamson
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Henteleff
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.forename: Julia K
authors.initials: JK
authors.lastname: Kofler
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000145:classification / Q000378:metabolism*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000145:classification / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D020662:Guanine Nucleotide Exchange Factors; D010446:Peptide Fragments; D020033:Protein Isoforms; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases