Neuropathology of cognitive decline in Lewy body disease

路易体病认知能力下降的神经病理学

基本信息

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

项目摘要

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

在神经读中，对多巴胺转运蛋白的PET扫描（^<11> C-CFT），葡萄糖代谢（^<18> F-FDG）和淀粉样蛋白（^<11> c-PIB）进行了相对检查。此外，招募了99例尸检病例，用于诊断DLB，PDD或PD进行本研究。所有病例均通过免疫细胞化学筛查抗ABTA（11-28），磷酸化的TAU（AT8）和磷酸化的α-核蛋白（Psync＃64）。从2008年至2010年，这项研究新招募了另外三例尸检病例。 DLB/PDD-PD的底物由新皮层，边缘系统和尾状核us中的新皮质斑块以及α-核蛋白沉积组成。 Lewy身体痴呆的底物，具有新皮质淀粉样蛋白阳性和负病……更多的是由边缘和神经元α-核蛋白，而不是纹状体α-链核素组成。从保守的8344尸检病例中选择了23例，具有足够的α-突触核蛋白沉积，没有明显的ABETA和TAU沉积，并将20例分类为边缘形式，将20例分类为新皮层形式。这些纯Lewy身体病例缺乏纹状体ABETA沉积。在临床宠物研究中，招募了DLB/PDD和PD病例的三个。证实了DLB/PDD患者的尾状核中cft摄取的降低。大约 ^<11> c-PIB PET扫描，三个PD病例根本缺乏皮质摄取，三个PDD/DLB病例中的两个也缺乏皮质摄取。这是无法计算纹状体 ^<11> c-cft摄取和 ^<11> c-pib之间的相关性。我们的数据证实了路易体疾病中痴呆的解剖学底物包括在边缘和新皮层结构中α-核蛋白的沉积。我们的研究还突出了钙核中α-核蛋白在酸性核中的沉积，这是Lewy身体痴呆的战略靶标，我们的研究无法确认先前的报道，即Abeta的纹状体沉积负责Lewy体内痴呆。对alpha-核蛋白沉积和改善的Dat scan scan scan in Cardied carlied netial delemen demenia indiemaia indiacia indiacia in vo yy demenia indieaia仍然是demenia indiemaia indiemaia demenia demenia indiaia indiaia necial demenia。