Department of Neurology, Clinical Research and Health Screening, Singapore General Hospital, Singapore.
Neurobiol Aging. 2011 Nov;32(11):1990-3. doi: 10.1016/j.neurobiolaging.2009.11.019. Epub 2009 Dec 16.
Overlapping neurodegenerative pathologies (including Alzheimer's disease, AD) have been described in Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations. We analyzed a LRRK2 PD (R1628P) risk variant in a group of 885 subjects comprising of AD and controls. The frequency of the R1628P allele was higher in AD compared to controls (3.5% vs. 1.6%, OR 2.3, 95 CI 1.2-4.4, p=0.018). In vitro, the mean percentage of apoptosis and cell death observed for the R1628P transfected human cell lines was higher compared to wild type 21.8 ± 1.9, vs. 17.1 ± 1.3, p<0.05, 30.2 ± 2.2 vs. 25.7 ± 1.3, p<0.05). The LRRK2 R1628P variant increases the risk of AD in our population and our in vitro findings suggest that it is a functional variant and predisposes to apoptosis.
在具有富亮氨酸重复激酶 2 (LRRK2) 突变的帕金森病 (PD) 患者中，已经描述了重叠的神经退行性病变（包括阿尔茨海默病，AD）。我们在包含 AD 和对照组的 885 名受试者的一组中分析了 LRRK2 PD（R1628P）风险变异体。与对照组相比，AD 中 R1628P 等位基因的频率更高（3.5%比 1.6%，OR 2.3，95%CI 1.2-4.4，p=0.018）。在体外，与野生型相比，转染了 R1628P 的人细胞系观察到的细胞凋亡和细胞死亡的平均百分比更高 21.8±1.9%比 17.1±1.3%，p<0.05，30.2±2.2%比 25.7±1.3%，p<0.05）。在我们的人群中，LRRK2 R1628P 变体增加了 AD 的风险，我们的体外研究结果表明它是一种功能性变体，并易导致细胞凋亡。
