共查询到6条相似文献,搜索用时 15 毫秒
1.
Murray PS Kirkwood CM Gray MC Ikonomovic MD Paljug WR Abrahamson EE Henteleff RA Hamilton RL Kofler JK Klunk WE Lopez OL Penzes P Sweet RA 《Neurobiology of aging》2012,33(12):2807-2816
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. 相似文献
2.
Identifying a biomarker for Alzheimer's disease that can be obtained from a blood sample has been a goal of researchers for many years. Over the past few years a number of investigators have studied several plasma biomarkers but most frequently plasma amyloid beta (Aβ)40 and Aβ42 while others have explored the use of genetic variants as biomarkers for diagnosis or risk. This review considers the cross-sectional and longitudinal data regarding plasma Aβ40 and Aβ42 as diagnostic biomarkers as well as risk biomarkers. Review of recent genome-wide association studies indicates as many as 10 genetic variants have been associated with susceptibility to Alzheimer's disease (AD). Further analysis suggests that these factors have modest effects on risk and are thus not helpful, as yet, in the diagnosis of disease. Until the function of these genes is understood, their role in risk and diagnosis will remain uncertain. Thus, there are several types of peripheral biomarkers under investigation, but more work is required before they can be deemed clinically useful. 相似文献
3.
Guiyou Liu Liangcai Zhang Rennan Feng Mingzhi Liao Yongshuai Jiang Zugen Chen Bin Zhao Keshen Li 《Neurobiology of aging》2013
Recently, the association between PICALM rs3851179 polymorphism and Alzheimer's disease (AD) was investigated in the Chinese population by 3 independent studies. However, both allele and genotype tests failed to reveal any association. The association was identified only in the APOEε4-negative subgroup. We think that the failure to replicate the association may be because of the relatively small sample size. In this research, we reinvestigated the association using all the samples from these 3 studies (n = 2486, and 1202 cases and 1284 control subjects). We failed to replicate this association between the rs3851179 polymorphism and AD in all samples and the APOEε4-negative subgroup. Our results indicate that rs3851179 may not be an AD susceptibility locus in the Chinese population and the APOEε4-negative subgroup. 相似文献
4.
Minglin Lang Qiangwang Fan Lei Wang Yajun Zheng Guiran Xiao Xiaoxi Wang Wei Wang Yi Zhong Bing Zhou 《Neurobiology of aging》2013
Disruption of copper homeostasis has been implicated in Alzheimer's disease (AD) during the last 2 decades; however, whether copper is a friend or a foe is controversial. Within a genetically tractable Drosophila AD model, we manipulated the expression of human high-affinity copper importer orthologous in Drosophila to explore the in vivo roles of copper ions in the development of AD. We found that inhibition of Ctr1C expression by RNAi in Aβ-expressing flies significantly reduced copper accumulation in the brains of the flies as well as ameliorating neurodegeneration, enhancing climbing ability, and prolonging lifespan. Interestingly, Ctr1C inhibition led to a significant increase in higher-molecular-weight Aβ42 forms in brain lysates, whereas it was accompanied by a trend of decreased expression of amyloid-β degradation proteases (including NEP1-3 and IDE) with age and reduced Cu-Aβ interaction-induced oxidative stress in Ctr1C RNAi flies. Similar results were obtained from inhibiting another copper importer Ctr1B and overexpressing a copper exporter DmATP7 in the nervous system of AD flies. These results imply that copper may play a causative role in developing AD, as either Aβ oligomers or aggregates were less toxic in a reduced copper environment or one with less copper binding. Early manipulation of brain copper uptake can have a great effect on Aβ pathology. 相似文献
5.
Andrea C Klaver Mary P Coffey Lynnae M Smith David A Bennett John M Finke Loan Dang David A Loeffler 《Journal of neuroinflammation》2011,8(1):1-11