Pathologic accumulation of α-synuclein and Aβ in Parkinson disease patients with dementia.
Pathologic accumulation of α-synuclein and Aβ in Parkinson disease patients with dementia.
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DOI：
10.1001/archneurol.2012.1608
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发表时间：
2012-10
影响因子：
--
通讯作者：
Perlmutter, Joel S.
中科院分区：
文献类型：
--
作者：
Kotzbauer, Paul T.;Cairns, Nigel J.;Campbell, Meghan C.;Willis, Allison W.;Racette, Brad A.;Tabbal, Samer D.;Perlmutter, Joel S.
目的：确定与帕金森病(PD)相关的个体病理蛋白沉积的相对贡献。对2005年2月24日至2010年7月25日的尸检患者进行分析，以确定单个病理性蛋白沉积(α-突触核蛋白、Aβ和tau)的分布和严重程度，采用常规的组织学和免疫组织化学分析方法，并建立神经病理分期标准。临床数据从用于所有帕金森病患者的电子病历系统中提取。在华盛顿大学运动障碍中心接受治疗的32名连续尸检患者，他们都有帕金森病的神经病理证实和痴呆史，无论就运动症状而言，痴呆症的发病时间是什么时候。与帕金森病相关的痴呆的三个病理亚型：(1)主要的联核症(Braak-Luy小体5-6期)(12[38%])，(2)主要的伴Aβ沉积的联核病(Braak-A-A样蛋白B-C期)，但有少量或没有皮质tau沉积(19[99%])，(3)合核病和A-β沉积至少伴中度的新皮质tau病(Braak-tau 5-6期；1[3%])。Kaplan-Meier和COX回归分析显示，伴Aβ沉积的联核症患者的生存期(从PD起病到死亡的年限和痴呆起病到死亡的年限)明显短于单纯联核病患者。与帕金森病相关的痴呆有两个主要的病理亚型：新皮质突触核病和新皮质突触核病伴Aβ沉积。伴有新皮质Aβ和tau沉积的阿尔茨海默病通常不会导致帕金森病痴呆。此外，在PD痴呆患者中，Aβ的积累与较低的生存率有关。还需要进一步的研究来前瞻性地确定α-突触核蛋白和Aβ积聚之间的联系，以及Aβ在帕金森病认知损害的发生和发展中的作用。
To determine the relative contributions of individual pathologic protein deposits associated with parkinson disease (PD). Autopsied patients were analyzed from February 24, 2005, through July 25, 2010, to determine the distribution and severity of individual pathologic protein deposits (α-synuclein, Aβ, and tau) using routine protocols for histologic and immunohistochemical analysis and established neuropathologic staging criteria. Clinical data were extracted from an electronic medical record system used for all patients with PD. Thirty-two consecutive autopsied patients treated at the Washington University Movement Disorders Center who had neuropathologic confirmation of PD and a history of dementia, regardless of the timing of the onset of dementia with respect to motor symptoms. Three pathologic subgroups of dementia associated with PD were identified: (1) predominant synucleinopathy (Braak Lewy body stages 5–6) (12 [38%]), (2) predominant synucleinopathy with Aβ deposition (Braak amyloid stages B–C) but minimal or no cortical tau deposition (19 [99%]), and (3) synucleinopathy and Aβ deposition with at least moderate neocortical tauopathy (Braak tau stages 5–6; 1 [3%]). Kaplan-Meier and Cox regression analyses revealed that patients with synucleinopathy plus Aβ deposition had significantly shorter survival (years from PD onset until death and years from dementia onset until death) than patients with synucleinopathy only. Dementia associated with PD has 2 major pathologic subgroups: neocortical synucleinopathy and neocortical synucleinopathy with Aβ deposition. Alzheimer disease with neocortical Aβ and tau deposition does not commonly cause dementia with PD. Furthermore, accumulation of Aβ is associated with lower survival rates in PD patients with dementia. Additional studies are needed to prospectively determine the association between α-synuclein and Aβ accumulation and the role of Aβ in the development and progression of cognitive impairment in PD.
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影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
9.9
作者：
Ballard, C.;Ziabreva, I.;Aarsland, D.
通讯作者：
Aarsland, D.
影响因子：
4.2
作者：
Ball, M;Braak, H;Khachaturian, Z
通讯作者：
Khachaturian, Z
影响因子：
9.9
作者：
Hurtig, HI;Trojanowski, JQ;Arnold, SE
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Arnold, SE
影响因子：
9.9
作者：
Burack, M. A.;Hartlein, J.;Cairns, N. J.
通讯作者：
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