Kestenbaum Meir, Alcalay Roy N
Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Adv Neurobiol. 2017;14:31-48. doi: 10.1007/978-3-319-49969-7_2.
LRRK2 mutations are present in 1% of all sporadic Parkinson's disease (PD) cases and 5% of all familial PD cases. Several mutations in the LRRK2 gene are associated with PD, the most common of which is the Gly2019Ser mutation. In the following review, we summarize the demographics and motor and non-motor symptoms of LRRK2 carriers with PD, as well as symptoms in non-manifesting carriers. The clinical features of LRRK2-associated PD are often indistinguishable from those of idiopathic PD on an individual basis. However, LRRK2 PD patients are likely to have less non-motor symptoms compared to idiopathic PD patients, including less olfactory and cognitive impairment. LRRK2-associated PD patients are less likely to report REM sleep behavior disorder (RBD) than noncarriers. In addition, it is possible that carriers are more prone to cancer than noncarriers with PD, but larger studies are required to confirm this observation. Development of more sensitive biomarkers to identify mutation carriers at risk of developing PD, as well as biomarkers of disease progression among LRRK2 carriers with PD, is required. Such biomarkers would help evaluate interventions, which may prevent PD among non-manifesting carriers, or slow down disease progression among carriers with PD.
LRRK2突变存在于所有散发性帕金森病（PD）病例的1%以及所有家族性PD病例的5%中。LRRK2基因的几种突变与PD相关，其中最常见的是Gly2019Ser突变。在以下综述中，我们总结了携带LRRK2的PD患者的人口统计学特征、运动和非运动症状，以及未表现出症状的携带者的症状。LRRK2相关PD的临床特征在个体层面上通常与特发性PD难以区分。然而，与特发性PD患者相比，LRRK2 PD患者可能有较少的非运动症状，包括较少的嗅觉和认知障碍。与未携带者相比，LRRK2相关PD患者报告快速眼动睡眠行为障碍（RBD）的可能性较小。此外，携带者可能比患有PD的未携带者更容易患癌症，但需要更大规模的研究来证实这一观察结果。需要开发更敏感的生物标志物来识别有患PD风险的突变携带者，以及LRRK2相关PD携带者中疾病进展的生物标志物。这些生物标志物将有助于评估干预措施，这些干预措施可能预防未表现出症状的携带者患PD，或减缓携带LRRK2的PD患者的疾病进展。
