期刊
NEUROBIOLOGY OF AGING
卷 33, 期 12, 页码 2807-2816出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.02.015
关键词
beta-amyloid; Kalirin; Psychosis; Alzheimer disease
资金
- Veterans Health Administration [5I01BX000452]
- National Institute on Aging [5P01AG014449, 5P50AG005133, 5R01AG027224]
- National Institute of Mental Health [5T32MH019986]
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 beta-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 beta-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 beta-amyloid(1-42)/beta-amyloid(1-40) ratio was increased, due primarily to reduced soluble beta-amyloid(1-40), and kalirin-7, -9, and -12 were reduced. These findings suggest that increased cortical beta-amyloid(1-42)/beta-amyloid(1-40) ratio and decreased kalirin expression may both contribute to the pathogenesis of psychosis in AD. Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据