背景:通常通过脑淀粉样蛋白正电子发射断层扫描/脑脊液(PET/CSF)筛选阿尔茨海默病(AD)试验参与者的资格,这是低效的,因为许多不是淀粉样蛋白阳性。使用基于血液的生物标志物可以减少屏幕故障。
方法:我们招募了755名非西班牙裔白人,115西班牙裔,112非西班牙裔黑人,和其他19名认知正常群体的少数民族参与者(n=417),轻度认知障碍(n=312),或轻度AD(n=272)参与者。血浆淀粉样蛋白β(Aβ)40,Aβ42,Aβ42/Aβ40,总tau,测量磷酸化tau(p-tau)181和p-tau217;淀粉样蛋白PET/CSF(n=956)确定淀粉样蛋白阳性。临床,血液生物标志物,并评估了与淀粉样蛋白状态相关的种族/种族差异。
结果:更大的减值,年龄较大,并且携带载脂蛋白E(apoE)ε4等位基因与更大的淀粉样蛋白负荷有关。所有乙醇组(p-tau217,≥0.8128)的血浆Aβ42/Aβ40,p-tau181和p-tau217的淀粉样状态的接受者工作特征曲线下面积均≥0.7117。年龄和apoEε4调整以及在定量极限之外的生物标志物值的估算提供了预测能力的微小改善。
结论:在临床试验中心招募的不同人群中,基于血液的生物标志物与淀粉样蛋白PET/CSF结果高度相关。
结论:淀粉样蛋白β(Aβ)42/Aβ40,磷酸化tau(p-tau)181和p-tau217血液生物标志物预测脑淀粉样蛋白阳性。P-tau217是脑淀粉样蛋白阳性的最强预测因子。来自不同种族的生物标志物,种族,和临床队列预测脑淀粉样蛋白阳性。社区人群与其他人群具有相似的阿尔茨海默病(AD)生物标志物水平。基于血液的测定的预筛选过程可以减少AD试验筛选失败的数量。
Alzheimer\'s disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many are not amyloid positive. Use of blood-based biomarkers may reduce screen failures.
We recruited 755 non-Hispanic White, 115 Hispanic, 112 non-Hispanic Black, and 19 other minority participants across groups of cognitively normal (n = 417), mild cognitive impairment (n = 312), or mild AD (n = 272) participants. Plasma amyloid beta (Aβ)40, Aβ42, Aβ42/Aβ40, total tau, phosphorylated tau (p-tau)181, and p-tau217 were measured; amyloid PET/CSF (n = 956) determined amyloid positivity. Clinical, blood biomarker, and ethnicity/race differences associated with amyloid status were evaluated.
Greater impairment, older age, and carrying an apolipoprotein E (apoE) ε4 allele were associated with greater amyloid burden. Areas under the receiver operating characteristic curve for amyloid status of plasma Aβ42/Aβ40, p-tau181, and p-tau217 with amyloid positivity were ≥ 0.7117 for all ethnoracial groups (p-tau217, ≥0.8128). Age and apoE ε4 adjustments and imputation of biomarker values outside limit of quantitation provided small improvement in predictive power.
Blood-based biomarkers are highly associated with amyloid PET/CSF results in diverse populations enrolled at clinical trial sites.
Amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p-tau)181, and p-tau 217 blood-based biomarkers predicted brain amyloid positivity. P-tau 217 was the strongest predictor of brain amyloid positivity. Biomarkers from diverse ethnic, racial, and clinical cohorts predicted brain amyloid positivity. Community-based populations have similar Alzheimer\'s disease (AD) biomarker levels as other populations. A prescreen process with blood-based assays may reduce the number of AD trial screen failures.