Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease.
Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease.
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DOI：
10.1001/jamaneurol.2014.2704
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发表时间：
2015-01
期刊：
影响因子：
29
通讯作者：
Marras, Connie
中科院分区：
文献类型：
--
作者：
Kalia, Lorraine V.;Lang, Anthony E.;Hazrati, Lili-Naz;Fujioka, Shinsuke;Wszolek, Zbigniew K.;Dickson, Dennis W.;Ross, Owen A.;Van Deerlin, Vivianna M.;Trojanowski, John Q.;Hurtig, Howard I.;Alcalay, Roy N.;Marder, Karen S.;Clark, Lorraine N.;Gaig, Carles;Tolosa, Eduardo;Ruiz-Martinez, Javier;Marti-Masso, Jose F.;Ferrer, Isidre;Lopez de Munain, Adolfo;Goldman, Samuel M.;Schuele, Birgitt;Langston, J. William;Aasly, Jan O.;Giordana, Maria T.;Bonifati, Vincenzo;Puschmann, Andreas;Canesi, Margherita;Pezzoli, Gianni;De Paula, Andre Maues;Hasegawa, Kazuko;Duyckaerts, Charles;Brice, Alexis;Stoessl, A. Jon;Marras, Connie
富含亮氨酸重复激酶 2 (LRRK2) 的突变是迄今为止已知的遗传性帕金森病 (PD) 的最常见原因。 LRRK2 突变携带者的临床特征通常与散发性 PD 患者没有区别。然而，一些与 LRRK2 突变相关的 PD 病例缺乏路易体 (LB)，这是 PD 的神经病理学标志。我们研究了 LB 的存在或缺失是否与 LRRK2 相关 PD 的不同临床特征相关。我们描述了截至 2013 年 10 月 37 例 LRRK2 相关 PD 病例的遗传、临床和神经病理学结果，其中包括 33 例已发表病例和 4 例未发表病例。在不同突变中，LRRK2 p.G2019S 突变最常与 LB 病理相关。认知障碍/痴呆、焦虑和直立性低血压的非运动特征与 LB 的存在相关。相反，主要运动表型与 LB 缺乏相关。据我们所知，这是一系列 LRRK2 相关 PD 病例中临床病理相关性的首次报告。这组选定的 PD 患者的研究结果表明，在缺乏 LB 的情况下也可能出现帕金森病运动特征。然而，LRRK2 相关 PD 中的 LB 病理学可能是更广泛的帕金森综合症（包括认知障碍）的标志。
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment.
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