Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore.
Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore.
Neurobiol Aging. 2018 Apr;64:157.e7-157.e9. doi: 10.1016/j.neurobiolaging.2017.11.012. Epub 2017 Nov 27.
Amyloid is the main pathological substrate of Alzheimer's disease (AD) and has been described in leucine-rich repeat kinase 2 (LRRK2) carriers with Parkinson's disease. LRRK2 has been linked with amyloid precursor protein pathways in neurodegeneration. Two common LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple Parkinson's disease cohorts. We hypothesized that R1398H and N551K may be protective in AD. In a case-control study involving 1390 subjects (719 controls and 671 AD cases), R1398H was demonstrated in 16.8% of AD cases compared to 16.7% in controls (odds ratio = 1.01, 95% confidence interval = 0.76-1.34, p = 0.94), whereas N551K was demonstrated in 17.3% of AD cases compared to 17.2% of controls (odds ratio = 1.00, 95% confidence interval = 0.76-1.32, p = 0.98). Overall, these results suggest that LRRK2 R1398H or N551K variants do not appear to modulate the risk of AD.
淀粉样蛋白是阿尔茨海默病（AD）的主要病理底物，已在富含亮氨酸重复激酶 2（LRRK2）的帕金森病携带者中描述。LRRK2 与神经退行性变中的淀粉样前体蛋白途径有关。两种常见的 LRRK2 变体，R1398H 和 N551K，已被证明在多个帕金森病队列中具有保护作用。我们假设 R1398H 和 N551K 在 AD 中可能具有保护作用。在一项涉及 1390 名受试者（719 名对照和 671 名 AD 病例）的病例对照研究中，AD 病例中 R1398H 的检出率为 16.8%，而对照组为 16.7%（比值比=1.01，95%置信区间=0.76-1.34，p=0.94），而 AD 病例中 N551K 的检出率为 17.3%，而对照组为 17.2%（比值比=1.00，95%置信区间=0.76-1.32，p=0.98）。总的来说，这些结果表明 LRRK2 R1398H 或 N551K 变体似乎不会调节 AD 的风险。
