使用全自动免疫分析法测量 CSF Aβ42/40 和 Aβ42/P-tau181 的稳健性，以检测与 AD 相关的结果。

Robustness of CSF Aβ42/40 and Aβ42/P-tau181 measured using fully automated immunoassays to detect AD-related outcomes.

机构信息

Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Department of Neurology, Skåne University Hospital, Lund, Sweden.

出版信息

Alzheimers Dement. 2023 Jul;19(7):2994-3004. doi: 10.1002/alz.12897. Epub 2023 Jan 21.

DOI:10.1002/alz.12897

PMID:36681387

Abstract

INTRODUCTION

This study investigated the comparability of cerebrospinal fluid (CSF) cutoffs for Elecsys immunoassays for amyloid beta (Aβ)42/Aβ40 or Aβ42/phosphorylated tau (p-tau)181 and the effects of measurement variability when predicting Alzheimer's disease (AD)-related outcomes (i.e., Aβ-positron emission tomography [PET] visual read and AD neuropathology).

METHODS

We studied 750 participants (BioFINDER study, Alzheimer's Disease Neuroimaging Initiative [ADNI], and University of California San Francisco [UCSF]). Youden's index was used to identify cutoffs and to calculate accuracy (Aβ-PET visual read as outcome). Using longitudinal variability in Aβ-negative controls, we identified a gray zone around cut-points where the risk of an inconsistent predicted outcome was >5%.

RESULTS

For Aβ42/Aβ40, cutoffs across cohorts were <0.059 (BioFINDER), <0.057 (ADNI), and <0.058 (UCSF). For Aβ42/p-tau181, cutoffs were <41.90 (BioFINDER), <39.20 (ADNI), and <46.02 (UCSF). Accuracy was ≈90% for both Aβ42/Aβ40 and Aβ42/p-tau181 using these cutoffs. Using Aβ-PET as an outcome, 8.7% of participants fell within a gray zone interval for Aβ42/Aβ40, compared to 4.5% for Aβ42/p-tau181. Similar findings were observed using a measure of overall AD neuropathologic change (7.7% vs. 3.3%). In a subset with CSF and plasma Aβ42/40, the number of individuals within the gray zone was ≈1.5 to 3 times greater when using plasma Aβ42/40.

DISCUSSION

CSF Aβ42/p-tau181 was more robust to the effects of measurement variability, suggesting that it may be the preferred Elecsys-based measure in clinical practice and trials.

摘要

简介

本研究旨在比较 Elecsys 免疫分析测定脑脊液（CSF）中淀粉样蛋白β（Aβ）42/Aβ40 或 Aβ42/磷酸化 tau（p-tau）181 的 cutoff 值，并评估其在预测阿尔茨海默病（AD）相关结局（即 Aβ-正电子发射断层扫描 [PET] 视觉阅读和 AD 神经病理学）时的测量变异性的影响。

方法

我们研究了 750 名参与者（BioFINDER 研究、阿尔茨海默病神经影像学倡议 [ADNI] 和加利福尼亚大学旧金山分校 [UCSF]）。使用约登指数确定 cutoff 值，并计算准确性（Aβ-PET 视觉阅读作为结局）。使用 Aβ 阴性对照的纵向变异性，我们确定了在 cutoff 值周围存在一个灰色区域，在此区域内，预测结果不一致的风险>5%。

结果

对于 Aβ42/Aβ40，各队列的 cutoff 值均<0.059（BioFINDER）、<0.057（ADNI）和<0.058（UCSF）。对于 Aβ42/p-tau181，cutoff 值分别为<41.90（BioFINDER）、<39.20（ADNI）和<46.02（UCSF）。使用这些 cutoff 值，Aβ42/Aβ40 和 Aβ42/p-tau181 的准确性均约为 90%。使用 Aβ-PET 作为结局，Aβ42/Aβ40 有 8.7%的参与者处于灰色区间，而 Aβ42/p-tau181 则有 4.5%。使用总体 AD 神经病理学变化的测量值也观察到了类似的发现（7.7%对 3.3%）。在具有 CSF 和血浆 Aβ42/40 的亚组中，当使用血浆 Aβ42/40 时，处于灰色区间的个体数量约为 1.5 至 3 倍。