Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Mov Disord. 2012 Jun;27(7):831-42. doi: 10.1002/mds.24962. Epub 2012 Mar 26.
Pathological data from autopsies genotyped for Parkinson's disease (PD)-related mutations in alpha-synuclein, Parkin, PINK1, DJ1, LRRK2, and glucocerebrosidase have accumulated in recent years. The aim of this review is to systematically review all pathological reports of mutation carriers and to identify pathological patterns and gaps in the currently available data. A systematic review of the English literature was done using the terms "Parkinson's disease," "brain pathology," "autopsy," the specific gene nomenclature, and any combination of the above. Most studies included reports of convenience samples: either cases that were preidentified as mutation carriers before autopsy or screens of Lewy body brain banks. Nineteen autopsies of alpha-synuclein mutation carriers, 49 of LRRK2 mutation carriers, nine of Parkin mutation carriers, one of a PINK1 mutation carrier, and 86 of glucocerebrosidase mutation carriers were identified. Most autopsies of alpha-synuclein, LRRK2 G2019S, and glucocerebrosidase mutation carriers demonstrated Lewy body pathology, as opposed to Parkin and LRRK2 non-G2019S mutation carriers. However, there was a marked variability in pathological findings, even among carriers of identical mutations. Pathological data from DJ1 mutation carriers, nonmanifesting mutation carriers (e.g., of LRRK2 mutations), and carriers of a single Parkin mutation were lacking. In gathering together all studies of PD autopsies with an identified genetic risk, this review highlights the wealth of information generated as well as shortcomings in the available data. In particular, there is a need for larger, unbiased pathological studies. Differential association of Lewy pathology with specific mutations may reflect heterogeneity in pathogenic mechanisms among the different PD-related genes.
近年来，积累了越来越多对帕金森病（PD）相关突变的α-突触核蛋白、Parkin、PINK1、DJ1、LRRK2 和葡萄糖脑苷脂酶进行基因分型的尸检的病理学数据。本综述的目的是系统地回顾所有突变携带者的病理学报告，并确定目前可用数据中的病理学模式和差距。使用“帕金森病”、“脑病理学”、“尸检”、特定基因命名法以及上述任何组合的术语，对英文文献进行了系统的回顾。大多数研究都包括方便样本的报告：要么是在尸检前预先确定为突变携带者的病例，要么是路易体脑库的筛查。鉴定了 19 名α-突触核蛋白突变携带者、49 名 LRRK2 突变携带者、9 名 Parkin 突变携带者、1 名 PINK1 突变携带者和 86 名葡萄糖脑苷脂酶突变携带者的尸检。大多数α-突触核蛋白、LRRK2 G2019S 和葡萄糖脑苷脂酶突变携带者的尸检显示路易体病理学，而不是 Parkin 和 LRRK2 非 G2019S 突变携带者。然而，即使在携带相同突变的携带者中，病理发现也存在明显的差异。DJ1 突变携带者、非表现型突变携带者（例如 LRRK2 突变）和单个 Parkin 突变携带者的病理学数据缺乏。在汇集所有具有明确遗传风险的 PD 尸检研究中，本综述突出了所产生的大量信息以及现有数据的不足。特别是，需要进行更大、无偏的病理学研究。Lewy 病理学与特定突变的不同关联可能反映了不同 PD 相关基因中致病机制的异质性。
