JPND GBA1 mutations in Parkinson disease: clinical and biochemical prodrome, risk profile and pathogenetic modelling for therapeutic intervention.

GBA1突变使帕金森病的风险增加20-30倍。英国小组已经建立了已公布的最大的GBA1突变携带者队列，纵向跟踪了100人，并开发了他们的临床和生化表型分析方案，以识别这一基因分层的高危人群中帕金森病的前驱特征。这项应用将建立在申请者之间现有的强大联系基础上，以增加这个英国队列，并将其与意大利和加拿大现有的GBA1突变携带者队列整合。在已建立的基于临床的队列中，协调对GBA1携带者的国际纵向评估，以确定先兆临床特征、认知、焦虑、抑郁)、生化表型，并识别那些转换为帕金森病的高风险人群。基因分层的个体群体，适合于未来针对那些患有帕金森病或帕金森病风险的GBA1突变患者的药物的临床试验。

GBA1 mutation increases PD risk by 20-30x.The UK group has established the largest published cohort of GBA1 mutation carriers with 100 followed longitudinally and has developed a protocol for their clinical and biochemical phenotyping to identify the prodromal features of PD in this genetically stratified high risk group.This application will build on the existing strong links between the applicants to increase and integrate this UK cohort with existing cohorts of GBA1 mutation carriers in Italy and Canada.Harmonised international longitudinal evaluation of GBA1 carriers in the established clinic based cohorts to determine prodromal clinical features , cognition, anxiety, depression), biochemical phenotype and identify those at high risk for conversion to PD. Genetically stratified group of individuals suitable for future clinical trials of agents targeted for those with GBA1 mutations with PD or at risk of PD.