文摘
摘要目的:CSF-to-autopsy研究调查脑脊液生物标志物的广告和广告之间的联系神经病理变化在大脑认知正常的捐赠者腰椎穿刺(LP)。
背景:脑脊液(CSF) Aβ的生物标志物1-42和p-tau181年的黄金标准检测阿尔茨海默病(AD)期间的生活。然而,脑脊液生物标志物临床端点和/或验证的研究主要使用Aβ-PET成像作为参考。一些CSF-to-autopsy研究存在,和现有的局限于后期的广告。体内检测早期AD神经病理学是至关重要的,因为它是预防和治疗干预的好时机。
设计/方法:国家阿尔茨海默氏症的大脑研究包括捐助者协调中心(NACC)脑脊液生物标记数据和正常的认知。由于缺乏标准化的CSF分析NACC,临死前的CSF Aβ浓度1-42,p-tau181年,t-tau测量使用三种分析方法:ELISA (n = 9), Luminex (n = 21),和Lumipulse (n = 49)。广告是基于神经病理学的诊断Braak≥3和CERAD≥2。逻辑回归测试每个脑脊液生物标志物和广告之间的关联状态,控制了年龄,性别,APOEɛ4、LP和死亡间隔和脑脊液化验方法。曲线下的面积(AUC)评估准确性歧视广告+ /广告−大脑捐助者。
结果:79年的大脑捐助者(n = 40岁,男性50.6%;n = 77, 97.5%的白人),26 (32.9%)autopsy-confirmed广告。平均年龄在LP是80.3 (SD = 6.1)年。Log-CSF p-tau181年/ Aβ1-42是广告的最优预测+(或= 15.86,95% CI -57.94 = 4.34, p <措施),并有一个歧视精度高(AUC = .903)。CSF p-tau181年是广告的第二好的预测状态(AUC =。832,OR=1.04, 95% CI=1.02–1.06, p<.001), followed by CSF Aβ1-42(AUC =。758,OR=0.995, 95% CI=0.992–0.999, p=0.005), and CSF t-tau that had the lowest discrimination accuracy (AUC=.746, OR=1.003, 95% CI=1.001–1.005, p=0.009).
结论:本研究验证CSF Aβ的有效性1-42和p-tau181年AD病理生理过程的早期检测,特别是p-tau比例181年/ Aβ1-42。
披露:Safransky小姐没有披露。Kaj Blennow已收到个人薪酬在500 - 4999美元的范围作为顾问生原体,轴突,JOMDD,罗氏公司,西门子。Kaj Blennow已收到个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会诺华,朱利叶斯临床。Kaj Blennow已收到个人薪酬在500 - 4999美元的范围服务扬声器MagQu管理局。Henrik Zetterberg已收到个人薪酬在500 - 4999美元的范围为罗氏公司担任顾问。Henrik Zetterberg已收到个人补偿的范围0 - 499美元为Abbvie担任顾问。Henrik Zetterberg已收到个人补偿的范围0 - 499美元为Acumen担任顾问。Henrik Zetterberg已收到个人补偿的范围0 - 499美元为AlzPATH担任顾问。Henrik Zetterberg已收到个人补偿的范围0 - 499美元为Annexon担任顾问。Henrik Zetterberg已收到个人补偿的范围0 - 499美元为Apellis担任顾问。 Henrik Zetterberg has received personal compensation in the range of $0-$499 for serving as a Consultant for Fujirebio. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Siemens Healthineers. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions. Yorghos Tripodis, 5406 has nothing to disclose. Brett Martin has nothing to disclose. Dr. Weller has nothing to disclose. Breton Asken has nothing to disclose. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eisai. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GE Healthcare. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer’s Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. The institution of Dr. Rabinovici has received research support from Genentech. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Topic Chair, Course Director and teacher with AAN. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Wendy Qiu has nothing to disclose. Dr. McKee has nothing to disclose. Dr. Stein has nothing to disclose. The institution of Michael Alosco, PHD has received research support from NIH.
