Neuropathology of cognitive decline in Lewy body disease

路易体病认知能力下降的神经病理学

• 批准号: 20390248
• 负责人: MURAYAMA Shigeo
• 金额: $ 12.23万
• 依托单位: Tokyo Metropolitan Institute of Gerontology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390248/
• 关键词: αシヌクレイン; タウ; βアミロイド; パーキンソン病; レビー小体型認知症; PIB PET; MRI; ドーパミン; アミロイドβ蛋白; レビー小体; 老人班; 神経原線維変化; 11C-PIB PET; バーチュアルスライド

We studied to identify anatomic substrates to explain dementia in Lewy body disease. Neuropathologically, consecutive autopsy cases were immunocytochemically studied for difference in Lewy body dementia (dementia with Lewy bodies : DLB and Parkinson disease with dementia) Parkinson disease without dementia. Neuroradiologically, PET scans for dopamine transporter (^<11>C-CFT), glucose metabolism (^<18>F-FDG) and amyloid (^<11>C-PIB) were comparatively examined.Overall, 99 autopsy cases with diagnosis DLB, PDD or PD were recruited for this study. All the cases were immunocytochemically screened for anti-Abta (11-28), phosphorylated tau (AT8) and phosphorylated alpha-synuclein (psyn#64). From 2008-2010, three more autopsy cases were newly recruited for this study. Substrates of DLB/PDD-PD consisted of neocortical plaque as well as alpha-sunuclein deposition in neocortex, limbic system and caudate nucleus. Substrates of Lewy body dementia with neocortical amyloid positive and negative case … More s consisted of limbic and necortical alpha-synuclein but not striatal alpha-synuclein. Twenty three cases of pure Lewy body dementia with sufficient alpha-synuclein deposition without significant Abeta and tau deposition were selected from consecutive 8344 autopsy cases and 20 were classified into limbic form and 3 into neocortical form. These pure Lewy body cases lacked striatal Abeta deposition.About clinical PET studies, three each of DLB/PDD and PD cases were recruited for the study. Decreased ^<11>C-CFT uptake in caudate nucleus of DLB/PDD patients were confirmed. About ^<11>C-PIB PET scans, the three PD cases lacked cortical uptake at all and two out of three PDD/DLB cases also lacked cortical uptake. Thus, the correlation between striatal ^<11>C-CFT uptake and ^<11>C-PIB could not be calculated.Our data confirmed anatomical substrate for dementia in Lewy body disease consisted of deposition of alpha-synuclein in limbic and neocortical structure. Our study also highlighted deposition of alpha-synuclein in caudate nucleus as strategic target for Lewy body dementia Our study could not confirm the previous reports that striatal deposition of Abeta is responsible for Lewy body dementia.Pathogenesis of alpha-synuclein deposition and decreased DAT scan in caudate nucleus in Lewy body dementia is yet to be clarified. Less

我们的研究是为了确定解剖学基础来解释路易体病中的痴呆。在神经病理学上，连续尸检病例进行了免疫细胞化学研究，以了解路易体痴呆（路易体痴呆：DLB和帕金森病痴呆）与帕金森病无痴呆的差异。对99例DLB、PDD或PD尸检病例进行神经影像学、PET显像及多巴胺转运体（^<11>C-CFT）、葡萄糖代谢（^<18>F-FDG）和淀粉样蛋白（^<11>C-PIB）检查。对所有病例进行抗Abta（11-28）、磷酸化tau（AT 8）和磷酸化α-突触核蛋白（psyn#64）的免疫细胞化学筛选。从2008年至2010年，本研究新招募了另外3例尸检病例。DLB/PDD-PD的底物包括新皮质斑块以及新皮质、边缘系统和尾状核中的α-sunuclein沉积。路易体痴呆伴新皮质淀粉样蛋白阳性和阴性病例的基质 ...更多信息 S由边缘和皮层α-突触核蛋白组成，但不包括纹状体α-突触核蛋白。从8344例尸检中筛选出23例α-突触核蛋白（α-synuclein，α-synuclein）大量沉积而无明显A β和tau蛋白沉积的单纯Lewy小体痴呆，其中边缘型20例，新皮质型3例。临床PET检查中，DLB/PDD和PD各3例。证实<11>DLB/PDD患者尾状核中C-CFT摄取减少。关于13 <11>C-PIB PET扫描，三个PD病例完全缺乏皮质摄取，并且三个PDD/DLB病例中的两个也缺乏皮质摄取。我们<11><11>的数据证实了路易体病痴呆的解剖学基础包括边缘系统和新皮质结构中α-突触核蛋白的沉积。我们的研究还强调了尾状核中α-突触核蛋白的沉积是路易体痴呆的战略目标我们的研究不能证实以前的报道，纹状体中的A β沉积是路易体痴呆的原因，尾状核中α-突触核蛋白沉积和DAT扫描减少的发病机制尚未阐明。少

项目成果

異常タンパク蓄積と神経変性、アルツハイマー病を中心に

专注于异常蛋白质积累、神经退行性变和阿尔茨海默病

• 发表时间: 2009
• 期刊: 実験医学 27
• 作者: 村山繁雄;齊藤祐子
• 通讯作者: 齊藤祐子

Prospective 10-year surveillance of human prion diseases in Japan Brain

日本对人类朊病毒疾病的前瞻性 10 年监测 Brain

• 发表时间: 2010
• 期刊: 133
• 作者: Nozaki I;Hamaguchi T;Sanjo N;Noguchi-Shinohara M;Sakai K;Nakamura Y;Sato T;Kitamoto T;Mizusawa H;Moriwaka F;Shiga Y;Kuroiwa Y;Nishizawa M;Kuzuhara S;Inuzuka T;Takeda M;Kuroda S;Abe K;Murai H;Murayama S;Tateishi J;Takumi I;Shirabe S
• 通讯作者: Shirabe S

Lewy body pathology involves cutaneous nerves

• DOI: 10.1097/nen.0b013e318186de48
• 发表时间: 2008-10-01
• 期刊: JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
• 影响因子: 3.2
• 作者: Ikemura, Masako;Saito, Yuko;Murayama, Shigeo
• 通讯作者: Murayama, Shigeo

Motor dysfunction and multi-domain mild cognitive impairment in association with FUS immunopositive intra-neuronal inclusions.

运动功能障碍和多域轻度认知障碍与 FUS 免疫阳性神经元内包涵体相关。

• 发表时间: 2010
• 作者: Takao M;Spina S;Spillantini MG;Murrell JR;Unverzagt FW;Farlow MR;Ghetti B.
• 通讯作者: Ghetti B.

The incidence and extent of Lewy- body related plpha- synucleinopathy in human aging olfactory bulb

人类衰老嗅球中路易体相关的α-突触核蛋白病的发生率和程度

• 发表时间: 2008
• 期刊: J Neuropath Exp Neurol 67
• 作者: Sengoku R;Saito Y;Ikemura M;Hatsuta H;Sakiyama Y. Sawabe M;Inoue K;Mochizuki H;Murayama S
• 通讯作者: Murayama S