Clinicopathological study of dementia : the Hisayama study

痴呆症的临床病理学研究：久山研究

• 批准号: 16300112
• 负责人: IWAKI Toru
• 金额: $ 8.06万
• 依托单位: KYUSHU UNIVERCITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300112/
• 关键词: dementia; Alzheimer's disease; dementia of Lewy body type; pathological criteria; alpha-synuclein; autopsy; cyclooxygenase; 脳血管性認知症; 神経原線維型認知症; 脳血管性痴呆; レビー小体型痴呆; 有病率; 痴呆

The Hisayama study is a prospective population-based clinicopathological cohort in a Japanese subrural community, Hisayama Town. Most deceased subjects have been examined by autopsy to confirm causes of death and to examine brain pathology. These features have allowed a reliable estimation of the frequency of neurodegenerative diseases relating dementia in a general population and for a detailed analysis of the difference between dementia and non-dementia. In this study we obtained following findings.(1)We have estimated the frequency of senile dementia of the neurofibrillary tangle type (SD-NFT), which was fourth frequent type of dementia (3.9%). We found that the number of NFTs in the hippocampus of SD-NFT cases did not necessarily exceed the degree of those in Alzheimer's disease and that total brain weights were significantly reduced to the same extent as Alzheimer's disease (AD), which suggest that not only the limbic NFT pathology but also some whole brain dysfunctions might caus … More e the mental deterioration.(2)To explore cyclooxygenase(COX)-2 expression in the hippocampus, we analyzed 45 consecutive autopsy subjects without dementia and 25 AD patients. The neuronal expression of COX-2 in the CA3 subdivision of the hippocampus, subiculum, entorhinal cortex and transentorhinal cortex were consistently observed in both non-demented and AD brains and COX-2 immunoreactivity correlated with age in non-demented brains. In AD patients, neurons of CA1 exhibited increased COX-2 immunoreactivity which correlated with the severity of AD pathology, this correlation was not apparent in non-demented subjects. The results suggest that COX-2 expression may be differentially regulated among subdivisions of the hippocampus and that elevated COX-2 expression in the CA1 of AD brains may be associated with AD pathology and thus cognitive dysfunction.(3)Dementia with Lewy bodies (DLB) ranks the third major dementia. To verify the validity of the revised criteria in 2005, we have analyzed 205 consecutive demented autopsy cases. LB pathology was present in 59 cases (28.8%). Female cases with DLB have a tendency for more severe LB pathology and Alzheimer-type pathology as well. The high likelihood cases and intermediate cases exhibited 0.44 and 0.94 of 3 clinical core features each on average, respectively. On the other hand, the low likelihood cases and the LB-negative cases showed only 0.19 and 0.18 each. In conclusion, it is appropriate to include both the high likelihood and intermediate cases for diagnosis of DLB. Less

久山研究是在日本郊区社区久山镇进行的一项基于人群的前瞻性临床病理学队列，大多数死亡受试者都经过尸检，以确认死亡原因并检查大脑病理学。这些特征可以对死亡频率进行可靠估计。在一般人群中与痴呆相关的神经退行性疾病以及对痴呆和非痴呆之间的差异的详细分析在这项研究中，我们获得了以下发现。（1）我们估计了神经原纤维老年痴呆的频率。缠结型（SD-NFT），这是第四种常见的痴呆类型（3.9％），我们发现SD-NFT病例海马中NFT的数量不一定超过阿尔茨海默病患者和整个大脑的程度。体重显着下降，程度与阿尔茨海默病（AD）相同，这表明不仅边缘系统 NFT 病理学而且一些全脑功能障碍也可能导致精神恶化。（2）探索我们分析了 45 名无痴呆的连续尸检受试者和 25 名 AD 患者的海马中环氧合酶（COX）-2 的表达情况，结果一致地观察到 COX-2 在海马 CA3 分区、下托、内嗅皮层和经内嗅皮层的神经元表达。非痴呆和 AD 大脑中的 COX-2 免疫反应性与非痴呆大脑中的年龄相关。 CA1 显示 COX-2 免疫反应性增加，这与 AD 病理的严重程度相关，但这种相关性在非痴呆受试者中并不明显。结果表明，COX-2 表达可能在海马各分区之间受到差异性调节，并且 COX-2 升高。 AD大脑CA1区的表达可能与AD病理进而导致认知功能障碍有关。(3)路易体痴呆(DLB)位列第三位主要痴呆。 验证修订后的标准的有效性。 2005年，我们分析了205例连续的痴呆LB病理，其中59例（28.8%）女性病例有更严重的LB病理和阿尔茨海默型病理的倾向。 3 个临床核心特征的平均分别为 0.44 和 0.94，而低可能性病例和 LB 阴性病例仅显示 0.19 和 0.94。总之，诊断 DLB 时应包括高可能性病例和中等可能性病例。

项目成果

Aluminum chloride does not facilitate deposition of human synthetic amyloid beta 1-42 peptide in the rat ventricular system of a short-term infusion model.

氯化铝不会促进人合成淀粉样β1-42肽在短期输注模型的大鼠心室系统中的沉积。

• 发表时间: 2005
• 期刊: Neuropathology 25
• 作者: Saito;H.;Somogyi J;Nakagawa Y
• 通讯作者: Nakagawa Y

Styrylbenzoazole derivatives for imaging of prion plaques and treatment of transmissible spongiform encephalopatheis.

苯乙烯基苯并唑衍生物，用于朊病毒斑成像和传染性海绵状脑病的治疗。

• 发表时间: 2006
• 期刊: J. Neurochem. 99
• 作者: Toyoshima Y;Onodera O;Yamada M;Tsuji S;Kozak JA;Kozak JA;Matsushita M;Michiue H;Matsushita M;Wu HY;Michiue H;Matsushita M;Wu HY;Michiue H;Noguchi H;Wu HY;Matsushita M;Arataki S;Michiue H;Fujimi K;Fujimi K;Fujimi K;Sasaki K;Noda K;Ishikawa K
• 通讯作者: Ishikawa K

Surface plasmon resonance analysis for the screening of anti-piron compounds.

用于筛选抗 Piron 化合物的表面等离子共振分析。

• 发表时间: 2006
• 期刊: Biol. Pharm. Bull. 29
• 作者: Toyoshima Y;Onodera O;Yamada M;Tsuji S;Kozak JA;Kozak JA;Matsushita M;Michiue H;Matsushita M;Wu HY;Michiue H;Matsushita M;Wu HY;Michiue H;Noguchi H;Wu HY;Matsushita M;Arataki S;Michiue H;Fujimi K;Fujimi K;Fujimi K;Sasaki K;Noda K;Ishikawa K;Kawatake S
• 通讯作者: Kawatake S