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Neuropathological study on atypical Alzheimer's disease and diffuse neurofibrillary tangles with calcification (DNTC)

非典型阿尔茨海默病和弥漫性神经原纤维缠结钙化（DNTC）的神经病理学研究

基本信息

批准号：
15591227
负责人：
TERADA Seishi
金额：
$ 1.41万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

1.We describe three cases of early- and one of late-onset Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history. In conclusion, (1)a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2)the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3)Abeta deposition can result in development of dementia without tau pathology, and (4)CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.2.Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.3.We performed an immunohistochemical study on tau-positive structures in neurodegenerative diseases, to clarify whether tau with the exon 3 insert was present in abnormal tau-positive structures. Abnormally phosphorylated tau containing the exon 3 insert is present in both PSP and CBD brain. Although most intraglial inclusions were negative for anti-E3 Ab, a few were positive. Therefore, tau isoforms containing the exon 3 insert are expressed at low levels in glial cells.

1.我们描述了3例早发性和1例迟发性阿尔茨海默病（AD）伴“棉絮状”斑块（CWP）但无家族史的病例。总之，（1）额叶综合征样人格改变可能是早发性CWP-AD的特征性临床特征之一，（2）CWP-AD中Abeta 40和Abeta 42的沉积模式比早老素-1相关病例的沉积模式更易变，（3）Abeta 40和Abeta 42的沉积可导致痴呆的发展而无tau病理学，（4）CWP-AD伴LB与其他几种伴LB的神经退行性疾病有一个共同的过程，涉及α-突触核蛋白和NAC沉积。2.最近，一项前瞻性双盲研究表明，塞来昔布，一种选择性环氧合酶-2（考克斯-2）抑制剂，与利培酮单药治疗相比，在精神分裂症患者急性期，利培酮治疗对阳性和阴性症状量表（PANSS）和所有子量表评分的改善显著更大。免疫组化定量分析表明，神经元考克斯-2的表达显着上调，在每个CA 1 -4区的阿尔茨海默病与对照组相比。相反，在精神分裂症组中，海马的任何分区中考克斯-2的表达都没有上调。这些结果表明塞来昔布可能通过考克斯-2非依赖性作用而影响精神分裂症的病理生理学，而不是通过抑制上调的考克斯-2蛋白的活性。3.我们对神经退行性疾病中tau蛋白阳性结构进行了免疫组织化学研究，以阐明带有外显子3插入的tau蛋白是否存在于异常的tau蛋白阳性结构中。含有外显子3插入物的异常磷酸化tau蛋白存在于PSP和CBD脑中。虽然大多数胶质内包涵体抗E3抗体呈阴性，少数呈阳性。因此，含有外显子3插入物的tau同种型在神经胶质细胞中以低水平表达。