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    • 1. 发明公开
    • 알쯔하이머 병의 진행에 대한 생체마커
    • 生物标志物对阿尔茨海默病的进展
    • KR1020090019848A
    • 2009-02-25
    • KR1020087030933
    • 2007-06-18
    • 노파르티스 아게
    • 헤,윤셍고메즈-만실라,발타자르메이어,조안로벨리,지오르지오쿤,라이네르알.빌베,그라엠
    • C12Q1/68
    • C12Q1/6883C12Q2600/156C12Q2600/158C12Q2600/172C12Q2600/118
    • The genetic polymorphism LRRK2 (leucine-rich repeat kinase 2)-T1602S is significantly associated with conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD), with the patients with TT genotype being at greater risk to progress to Alzheimer's disease. The LRRK2-T2352 also showed a trend for conversion to Alzheimer's disease, with the patients with CC genotype tending to progress to Alzheimer's disease. Similar to the APOE-E4 allele, in the presence of a BuChE-K variant, LRRK2-T1602S and LRRK2-T2352 showed a greater association with the rate of conversion from mild cognitive impairment to Alzheimer's disease. In another study with placebo-treated Alzheimer's disease patients, LRRK2-T1602S and LRRK2-T2352 showed a same trend of association. The Alzheimer's disease patients with TT genotype of LRRK2-T1602S or CC genotype of LRRK2-T2352 tended to decline faster on cognitive performance over 6 months, especially in the presence of a BuChE-K variant. The association between the two common LRRK2 polymorphisms and Alzheimer's disease progression shows that LRRK2 may play a role in Alzheimer's disease pathogenesis, especially disease progression, and that polymorphisms of LRRK2 can be used as biomrkers of this progression.
    • 遗传多态性LRRK2(富含亮氨酸的重复激酶2)-T1602S与轻度认知障碍(MCI)转变为阿尔茨海默病(AD)显着相关,TT基因型患者进入阿尔茨海默氏病的风险更大。 LRRK2-T2352也显示出转化为阿尔茨海默病的趋势,CC基因型患者往往进展为阿尔茨海默氏病。 与APOE-E4等位基因相似,在BuChE-K变体存在下,LRRK2-T1602S和LRRK2-T2352显示与从轻度认知障碍转变为阿尔茨海默氏病的速率更大的关联。 在安慰剂治疗的阿尔茨海默病患者的另一项研究中,LRRK2-T1602S和LRRK2-T2352显示出相同的关联趋势。 具有LRRK2-T1602S的TT基因型或LRRK2-T2352的CC基因型的阿尔茨海默氏病患者在6个月以上的认知功能上往往更快下降,特别是在存在BuChE-K变体的情况下。 两种常见的LRRK2多态性与阿尔茨海默病进展的关系表明,LRRK2可能在阿尔茨海默氏病发病机制中发挥重要作用,特别是疾病进展,LRRK2的多态性可作为这一进展的生物学家。