文摘
摘要目的:验证和探索metabolomics-based等离子体生物标志物的帕金森病(PD)LRRK2和GBA航空公司相比,零星的PD患者PPMI参与者。
背景:前血浆代谢组学分析PD(+)和PD(−)科目包括LRRK2和GBA突变携带者复制显著差异在PD caffeine-related代谢物(+)和PD(−)和显示,GBA减少GCase活动载体等离子体和非承运人(Crotty MDS马德里2022)。在这里,我们报告额外的探索性分析与疾病和遗传有关的代谢组学概要文件状态。
设计/方法:等离子体从629年PPMI参与者选择基于PD(+ /−)和遗传状态(一个GBA或LRRK2突变或没有)被液相色谱与质谱分析。298年等离子体分析物符合报告标准。标准化的分析物的水平组间比较使用健壮的ANCOVA模型log2分析物的水平作为因变量,年龄,性别,PD状态、遗传状态,使用左旋多巴,及其交互作为独立的变量。
结果:预测结果复制PD协会ergothioneine和咖啡因代谢物GBA联想glucosylsphingosine (GlcSph)。LRRK2地位是独特与增加循环水平docosahexanoic酸(DHA)和其他脂质类含有DHA包括lysophosphatidylcholine (LPC)和bis (monoacylglycero)磷酸(BMP)。此外,温和但非常具体的联系减少4-trimethylaminobutanal (TMABA;蛋白质lysine-derived分解代谢物)GBA的地位。
结论:代谢与PD高度不同的联想,LRRK2和GBA状态,可能描述基础生物学的差异。虽然生活方式/异型生物质概要文件主要在PD,独特的GlcSph TMABA和之间的联系GBA溶酶体功能的状态与预期的改变。广泛改变DHA含有脂质,包括大脑所需LPC-DHA DHA,只观察到LRRK2 (+)主题,独立的疾病和左旋多巴的地位。占主导地位的LRRK2端依赖血脂水平展示小说系统性DHA体内平衡和之间的联系LRRK2多态性。需要进一步的研究来阐明这些发现的潜在因果影响。
披露:Huntwork-Rodriguez博士已经收到个人赔偿作为一个员工的德纳里峰的疗法。Huntwork-Rodriguez博士股票德纳里治疗。Huntwork-Rodriguez博士收到发现或技术知识产权利益有关卫生保健。Suh博士已经收到个人赔偿作为一个员工的德纳里峰的疗法。Crotty博士的机构已收到研究帕金森基金会的支持。Maciuca先生已经收到个人赔偿作为一个员工的德纳里峰的疗法。Maciuca先生曾获得股票或德纳里峰疗法的所有者权益。Macklin博士的机构已收到个人薪酬在500 - 4999美元的范围为AI疗法作为顾问。Macklin博士已经收到个人薪酬在500 - 4999美元的范围为Cortexyze担任顾问。Macklin博士已经收到个人薪酬在500 - 4999美元的范围作为顾问追逐疗法。 Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoparkinson Healthcare LLC. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Macklin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Macklin has received research support from Biohaven. The institution of Dr. Macklin has received research support from Clene Nanomedicine. The institution of Dr. Macklin has received research support from Mitsubishi Tanabe Pharmaceuticals America. The institution of Dr. Macklin has received research support from Prilenia. The institution of Dr. Macklin has received research support from UCB Ra Pharma. The institution of Dr. Macklin has received research support from Revalesio. The institution of Dr. Macklin has received research support from Seelos. The institution of Dr. Macklin has received research support from Calico. The institution of Dr. Macklin has received research support from Denali. The institution of Dr. Macklin has received research support from NeuroDex. The institution of Dr. Macklin has received research support from Alector. Dr. Davis has received personal compensation for serving as an employee of Denali Therapeutics. Mr. Alkabsh has received personal compensation for serving as an employee of Denali Therepeutics. An immediate family member of Rachit Bakshi has received personal compensation for serving as an employee of Partner Therapeutics. The institution of Rachit Bakshi has received research support from MJFF. Dr. Chen has nothing to disclose. Dr. Molsberry has nothing to disclose. The institution of Dr. Ascherio has received research support from NIH and US Department of Defense . The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial Biotech (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen (indirectly, as a service of the Parkinson Study Group service). The institution of Dr. Schwarzschild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB (indirectly, as a service of the Parkinson Study Group service). Dr. Schwarzschild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. The institution of Dr. Schwarzschild has received research support from NIH. The institution of Dr. Schwarzschild has received research support from Parkinson’s Foundation. The institution of Dr. Schwarzschild has received research support from Michael J Fox Foundation. The institution of Dr. Schwarzschild has received research support from Farmer Family Foundation. Dr. Schwarzschild has a non-compensated relationship as a Chair, Executive Committee with the Parkinson Study Group that is relevant to AAN interests or activities.
