淀粉样β、tau 和 α-突触核蛋白作为脑淀粉样血管病患者的潜在血液生物标志物的作用。

The Role of Amyloid-β, Tau, and α-Synuclein Proteins as Putative Blood Biomarkers in Patients with Cerebral Amyloid Angiopathy.

机构信息

Department of Pharmacy, University of Pisa, Pisa, Italy.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

出版信息

J Alzheimers Dis. 2022;89(3):1039-1049. doi: 10.3233/JAD-220216.

DOI:10.3233/JAD-220216

PMID:35964181

Abstract

BACKGROUND

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β protein (Aβ) within brain blood vessels that develops in elderly people and Alzheimer's disease (AD) patients. Therefore, the investigation of biomarkers able to differentiate CAA patients from AD patients and healthy controls (HC) is of great interest, in particular in peripheral fluids.

OBJECTIVE

The current study aimed to detect the neurodegenerative disease (ND)-related protein (i.e., Aβ1-40, Aβ1-42, tau, and α-synuclein) levels in both red blood cells (RBCs) and plasma of CAA patients and HC, evaluating their role as putative peripheral biomarkers for CAA.

METHODS

For this purpose, the proteins' concentration was quantified in RBCs and plasma by homemade immunoenzymatic assays in an exploratory cohort of 20 CAA patients and 20 HC.

RESULTS

The results highlighted a significant increase of Aβ1-40 and α-synuclein concentrations in both RBCs and plasma of CAA patients, while higher Aβ1-42 and t-tau levels were detected only in RBCs of CAA individuals compared to HC. Moreover, Aβ1-42/Aβ1-40 ratio increased in RBCs and decreased in plasma of CAA patients. The role of these proteins as candidate peripheral biomarkers easily measurable with a blood sample in CAA needs to be confirmed in larger studies.

CONCLUSION

In conclusion, we provide evidence concerning the possible use of blood biomarkers for contributing to CAA diagnosis and differentiation from other NDs.

摘要

背景

脑淀粉样血管病（Cerebral amyloid angiopathy，CAA）是一种脑血管疾病，其特征是淀粉样β蛋白（amyloid-β protein，Aβ）在脑血管内沉积，多见于老年人和阿尔茨海默病（Alzheimer's disease，AD）患者。因此，研究能够区分 CAA 患者与 AD 患者和健康对照者（healthy controls，HC）的生物标志物具有重要意义，特别是在外周体液中。

目的

本研究旨在检测 CAA 患者和 HC 的红细胞（red blood cells，RBCs）和血浆中神经退行性疾病（neurodegenerative disease，ND）相关蛋白（即 Aβ1-40、Aβ1-42、tau 和 α-synuclein）的水平，评估其作为 CAA 潜在外周生物标志物的作用。

方法

为此，在一个包含 20 名 CAA 患者和 20 名 HC 的探索性队列中，通过自制的免疫酶联测定法分别检测 RBCs 和血浆中这些蛋白质的浓度。

结果

结果表明，CAA 患者的 RBCs 和血浆中 Aβ1-40 和 α-synuclein 浓度显著升高，而 CAA 个体的 RBCs 中 Aβ1-42 和 t-tau 水平更高。此外，RBCs 中 Aβ1-42/Aβ1-40 比值增加，而血浆中则降低。这些蛋白作为 CAA 外周生物标志物的作用，需要在更大的研究中进一步证实。