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

1.我们描述了三例早发性阿尔茨海默病(AD)和一例晚发性阿尔茨海默病(AD)，其中有棉花斑块(CWPs)，但没有家族史。综上所述，(1)额叶综合征样人格改变可能是早发性CWP-AD的典型临床特征之一；(2)Abeta40和Abeta42在CWP-AD中的沉积模式比与早老素-1相关的病例更具多样性；(3)Abeta沉积可以导致无tau病理的痴呆的发展；(4)CWP-AD伴LBS和其他几种伴有LBS的神经退行性疾病具有共同的过程，涉及α-突触核蛋白和NAC的沉积。2.最近，一项前瞻性的双盲研究表明，选择性环氧合酶-2(COX-2)抑制剂eccoxib的辅助治疗与单用利培酮治疗相比，精神分裂症患者急性期在阳性和阴性症状量表(PANSS)和所有分量表上的得分改善显著。免疫组织化学定量分析显示，与对照组相比，阿尔茨海默病患者脑内各CA1-4区神经元COX-2的表达均显著上调。相比之下，在精神分裂症组的海马区，COX-2的表达没有上调。这些结果表明，塞来昔布可能通过COX-2非依赖性作用而不是通过抑制上调的COX-2蛋白的活性来影响精神分裂症的病理生理。3.我们对神经退行性疾病中的tau阳性结构进行了免疫组织化学研究，以阐明在异常的tau阳性结构中是否存在带有外显子3的tau。PSP和CBD脑中均存在含有外显子3插入的异常磷酸化tau。虽然大部分胶质内包涵体抗E3抗体均为阴性，但少数呈阳性反应。因此，含有外显子3插入的tau亚型在神经胶质细胞中低水平表达。

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.