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

我们研究确定解剖底物来解释路易体病痴呆。神经病理学上，连续尸检病例免疫细胞化学研究路易体痴呆（路易体痴呆：DLB和帕金森病伴痴呆）帕金森病无痴呆的差异。神经放射学上，PET扫描多巴胺转运蛋白（^<11>C-CFT），葡萄糖代谢（^<18>F-FDG）和淀粉样蛋白（^<11>C-PIB）进行比较检查。总体而言，本研究招募了99例诊断为DLB、PDD或PD的尸检病例。所有病例均进行抗abta（11-28）、磷酸化tau （AT8）和磷酸化α -突触核蛋白（psyn#64）的免疫细胞化学筛查。2008-2010年，本研究又新招募了3例尸检病例。DLB/PDD-PD的底物包括新皮层斑块以及新皮层、边缘系统和尾状核中的α - sunnuclein沉积。新皮层淀粉样蛋白阳性和阴性的路易体痴呆的底物由边缘和皮层α -突触核蛋白组成，而纹状体α -突触核蛋白不存在。从连续8344例尸检病例中选取了23例具有充足α -突触核蛋白沉积，但无明显的β和tau沉积的纯路易体痴呆患者，将其分为边缘型20例，新皮质型3例。这些纯路易体病例缺乏纹状体β沉积。关于临床PET研究，DLB/PDD和PD病例各3例被纳入研究。证实DLB/PDD患者尾状核C-CFT摄取减少^<11>。大约^<11 b> C-PIB PET扫描，3例PD患者完全缺乏皮质摄取，3例PDD/DLB患者中2例也缺乏皮质摄取。因此，纹状体^<11>C-CFT摄取与^<11>C-PIB之间的相关性无法计算。我们的数据证实了路易体病痴呆的解剖学基础包括α -突触核蛋白在边缘和新皮质结构中的沉积。我们的研究还强调了尾状核α -突触核蛋白的沉积是路易体痴呆的战略靶点。我们的研究不能证实先前报道的纹状体沉积是路易体痴呆的原因。路易体痴呆尾状核α -突触核蛋白沉积和DAT扫描减少的发病机制尚不清楚。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