Pletnikova Olga, West Neva, Lee Michael K, Rudow Gay L, Skolasky Richard L, Dawson Ted M, Marsh Laura, Troncoso Juan C
Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Ross Building 558, Baltimore, MD 21205, USA.
Neurobiol Aging. 2005 Aug-Sep;26(8):1183-92. doi: 10.1016/j.neurobiolaging.2004.10.006. Epub 2004 Dec 28.
In order to understand better the neuropathological substrate of dementia in Parkinson's disease (PD) and to examine its interactions with Alzheimer's disease (AD), we examined autopsy brains from 21 cases of PD and Lewy body disease (LBD) with dementia. We separated brains in two groups according to the presence of Abeta deposits. In brains without Abeta, we found few or no Lewy bodies (LB) in the cerebral cortex. By contrast, in brains with Abeta, we observed significant increases in LB in the cerebral cortex (p < 0.01) and alpha-synuclein immunoreactive lesions in the cingulate cortex (p < 0.01). Immunoblots of alpha-synuclein from cingulate cortex in brains with Abeta showed significantly higher levels of insoluble alpha-synuclein compared to brains without Abeta. Our observations indicate that in cases of PD with dementia, the neocortex is not necessarily involved by LB. Furthermore, the presence of Abeta deposits in the cerebral cortex was associated with extensive alpha-synuclein lesions and higher levels of insoluble alpha-synuclein. This suggests that Abeta enhances the development of cortical alpha-synuclein lesions in cases of PD.
为了更好地理解帕金森病（PD）痴呆的神经病理学基础，并研究其与阿尔茨海默病（AD）的相互作用，我们检查了21例患有痴呆的PD和路易体病（LBD）患者的尸检大脑。我们根据β淀粉样蛋白（Aβ）沉积物的存在将大脑分为两组。在没有Aβ的大脑中，我们在大脑皮层中发现很少或没有路易小体（LB）。相比之下，在有Aβ的大脑中，我们观察到大脑皮层中的LB显著增加（p < 0.01），扣带回皮层中的α-突触核蛋白免疫反应性病变也显著增加（p < 0.01）。与没有Aβ的大脑相比，有Aβ的大脑扣带回皮层中α-突触核蛋白的免疫印迹显示不溶性α-突触核蛋白水平显著更高。我们的观察结果表明，在患有痴呆的PD病例中，新皮层不一定被LB累及。此外，大脑皮层中Aβ沉积物的存在与广泛的α-突触核蛋白病变以及更高水平的不溶性α-突触核蛋白有关。这表明在PD病例中，Aβ会促进皮层α-突触核蛋白病变的发展。
