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

我们研究确定了神经病理学上痴呆的解剖学基础，对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 和帕金森病伴痴呆）、无痴呆的帕金森病。用于多巴胺转运蛋白 (^<11>C-CFT)、葡萄糖代谢 (^<18>F-FDG) 和淀粉样蛋白(^ 11 C-PIB)进行了比较检查。总共，本研究招募了99例尸检诊断为DLB、PDD或PD的病例，所有病例均进行了抗Abta(11-28)、磷酸化tau()的免疫细胞化学筛查。 AT8）和磷酸化α-突触核蛋白（psyn＃64）从2008年至2010年，为此新招募了三个尸检病例。 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，而新皮质淀粉样蛋白阳性和阴性病例的路易体痴呆的底物包括边缘和坏死皮质 α。 -突触核蛋白，但不是纹状体 α-突触核蛋白。23 例纯路易体痴呆，具有足够的 α-突触核蛋白沉积，但没有显着的 Abeta 和 tau 蛋白。从连续8344例尸检病例中选取沉积物，20例分类为边缘型，3例分类为新皮质型，这些纯路易体病例缺乏纹状体Abeta沉积。关于临床PET研究，DLB/PDD和PD病例各招募3例。 .DLB/PDD患者尾状核中^<11>C-CFT摄取减少关于^<11>C-PIB PET扫描得到证实。三个PD病例根本缺乏皮质摄取，并且三分之二的PDD/DLB病例也缺乏皮质摄取。因此，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病痴呆的解剖学基础包括边缘和新皮质结构中α-突触核蛋白的沉积，我们的研究还强调尾状核中α-突触核蛋白的沉积是战略性的。路易体痴呆的目标 我们的研究无法证实之前的报道，即纹状体沉积 Abeta 是路易体痴呆的原因。路易体痴呆尾状核中 α-突触核蛋白沉积和 DAT 扫描减少的发病机制尚未阐明。

项目成果

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
• 作者: Nozaki I; Hamaguchi T; Sanjo N; Noguchi
• 通讯作者: Noguchi

Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n.

31 型脊髓小脑共济失调与含有 (TGGAA)n 的“插入”五核苷酸重复有关。

• 发表时间: 2009
• 作者: Sato N; Amino T; Kobayashi K; Asakawa S; Ishiguro T; Tsunemi T; Takahashi M; Matsuura T; Flanigan KM; Iwasaki S; Ishino F; Saito Y; Murayama S; Yoshida M; Hashizume Y; Takahashi Y; Tsuji S; Shimizu N; Toda T; Ishikawa K; Mizusawa H
• 通讯作者: Mizusawa H

リハの基礎となる動的神経病理(画像・病理連関). 頭部外傷

动态神经病理学（影像学/病理学联动）作为头部创伤康复的基础。

• 发表时间: 2009
• 作者: 村山繁雄;齊藤祐子;徳丸阿耶
• 通讯作者: 徳丸阿耶

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
• 作者: 村山繁雄;齊藤祐子
• 通讯作者: 齊藤祐子

α-Synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure autonomic failure.

皮肤活检显示纯自主神经衰竭时皮肤神经纤维中 α-突触核蛋白积聚。

• 发表时间: 2010
• 作者: Shishido T; Ikemura M; Obi T; Yamazaki K; Terada T; Sugiura A; Saito Y; Murayama S; Mizoguchi K
• 通讯作者: Mizoguchi K