超敏检测血浆淀粉样蛋白-β作为阿尔茨海默病风险认知正常老年人的生物标志物。

Ultrasensitive Detection of Plasma Amyloid-β as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer's Disease.

机构信息

Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.

School of Medical Health and Sciences, Edith Cowan University, Joondalup, WA, Australia.

出版信息

J Alzheimers Dis. 2019;71(3):775-783. doi: 10.3233/JAD-190533.

DOI:10.3233/JAD-190533

PMID:31424403

Abstract

BACKGROUND

Aberrant amyloid-β (Aβ) deposition in the brain occurs two decades prior to the manifestation of Alzheimer's disease (AD) clinical symptoms and therefore brain Aβ load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain Aβ deposition, attractive candidates for investigation as surrogate markers.

OBJECTIVE

Investigation of plasma Aβ as a surrogate marker for brain Aβ deposition in cognitively normal elderly individuals.

METHODS

Plasma Aβ40 and Aβ42 concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain Aβ deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer 18F-Florbetaben, plasma Aβ was compared between 32 participants assessed to have low brain Aβ load (Aβ-, SUVR <1.35) and 63 assessed to have high brain Aβ load (Aβ+, SUVR ≥1.35).

RESULTS

Plasma Aβ42/Aβ40 ratios were lower in the Aβ+ group compared to the Aβ-group. Plasma Aβ40 and Aβ42 levels were not significantly different between Aβ-and Aβ+ groups, although a trend of higher plasma Aβ40 was observed in the Aβ+ group. Additionally, plasma Aβ42/Aβ40 ratios along with the known AD risk factors, age and APOEɛ4 status, resulted in Aβ+ participants being distinguished from Aβ-participants based on an area under the receiver operating characteristic curve shown to be 78%.

CONCLUSION

Plasma Aβ ratios in this study are a potential biomarker for brain Aβ deposition and therefore, for preclinical AD. However, this method to measure plasma Aβ needs further development to increase the accuracy of this promising AD blood biomarker.

摘要

背景

异常的淀粉样蛋白-β（Aβ）在大脑中的沉积发生在阿尔茨海默病（AD）临床症状出现前二十年，因此使用 PET 测量的大脑 Aβ 负荷被认为是 AD 早期诊断的金标准生物标志物。然而，由于 PET 的成本较高，反映大脑 Aβ 沉积的血液标志物成为替代标志物的研究热点。

目的

研究认知正常老年人血浆 Aβ作为大脑 Aβ 沉积的替代标志物。

方法

使用超灵敏单分子阵列（Simoa）检测 95 例认知正常老年人的血浆 Aβ40 和 Aβ42 浓度，这些老年人都接受了 PET 检查以评估大脑 Aβ 沉积。根据 PET 成像获得的标准摄取值比值（SUVR），使用示踪剂 18F-Florbetaben，比较 32 名被评估为大脑 Aβ 负荷低（Aβ-，SUVR＜1.35）和 63 名被评估为大脑 Aβ 负荷高（Aβ+，SUVR≥1.35）的参与者之间的血浆 Aβ。

结果

Aβ+组的血浆 Aβ42/Aβ40 比值低于 Aβ-组。Aβ-和 Aβ+组之间的血浆 Aβ40 和 Aβ42 水平没有显著差异，但在 Aβ+组中观察到血浆 Aβ40 水平较高的趋势。此外，血浆 Aβ42/Aβ40 比值以及已知的 AD 风险因素（年龄和 APOEɛ4 状态）可将 Aβ+参与者与 Aβ-参与者区分开来，ROC 曲线下面积表明区分能力为 78%。