散发性和遗传性脑淀粉样血管病患者脑脊液淀粉样蛋白β 38、40、42 和 43 水平降低。

Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy.

机构信息

Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands.

Medical Image Analysis Center and Qbig, Department of Biomedical Engineering, University of Basel, Basel, Switzerland.

出版信息

Ann Neurol. 2023 Jun;93(6):1173-1186. doi: 10.1002/ana.26610. Epub 2023 Feb 20.

DOI:10.1002/ana.26610

PMID:36707720

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10238617/

Abstract

OBJECTIVE

Vascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42, and Aβ43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).

METHODS

Aβ peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).

RESULTS

We found decreased levels of all Aβ peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for Aβ42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82-0.99; for validation: 0.94, 95% CI = 0.89-0.99) and Aβ43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88-1.00; for validation: 0.91, 95% CI = 0.83-1.0). All Aβ peptides except Aβ43 were also decreased in sCAA compared to AD (CSF Aβ38: AUC = 0.82, 95% CI = 0.71-0.93; CSF Aβ40: AUC = 0.88, 95% CI = 0.80-0.96; CSF Aβ42: AUC = 0.79, 95% CI = 0.66-0.92).

INTERPRETATION

A combined biomarker panel of CSF Aβ38, Aβ40, Aβ42, and Aβ43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023;93:1173-1186.

摘要

目的

血管淀粉样β（Aβ）的积累是脑淀粉样血管病（CAA）的标志。CAA 患者的脑脊液（CSF）组成可能作为 CAA 的诊断生物标志物。我们研究了 CAA 患者（sCAA）、遗传性荷兰型 CAA（D-CAA）和阿尔茨海默病（AD）患者中 Aβ38、Aβ40、Aβ42 和 Aβ43 肽的诊断潜力。

方法

使用免疫分析方法在发现组（26 例 sCAA 患者和 40 名对照）、验证组（40 例 sCAA 患者、40 例 AD 患者和 37 名对照）和 22 例 D-CAA 患者和 54 名对照中定量 Aβ 肽。使用具有 95%置信区间（CI）的接收器操作特征曲线计算曲线下面积（AUC）以确定诊断准确性。

结果

与对照组相比，我们发现 sCAA 患者和 D-CAA 患者的所有 Aβ 肽水平均降低。Aβ42 的差异最为明显（发现组 sCAA 与对照组的 AUC：0.90，95%CI=0.82-0.99；验证组：0.94，95%CI=0.89-0.99）和 Aβ43（发现组 sCAA 与对照组的 AUC：0.95，95%CI=0.88-1.00；验证组：0.91，95%CI=0.83-1.0）。与 AD 相比，除 Aβ43 外，所有 Aβ 肽在 sCAA 中均降低（CSF Aβ38：AUC=0.82，95%CI=0.71-0.93；CSF Aβ40：AUC=0.88，95%CI=0.80-0.96；CSF Aβ42：AUC=0.79，95%CI=0.66-0.92）。