Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
Decreased Cerebrospinal Fluid Amyloid β 38, 40, 42, and 43 Levels in Sporadic and Hereditary Cerebral Amyloid Angiopathy
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DOI：
10.1002/ana.26610
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发表时间：
2023-02-20
影响因子：
11.2
通讯作者：
Verbeek, Marcel M.
中科院分区：
文献类型：
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作者：
De Kort, Anna M.;Kuiperij, H. Bea;Verbeek, Marcel M.
目的：血管淀粉样蛋白（Aβ）积聚是脑淀粉样血管病（CAA）的标志。 CAA患者的脑脊液（CSF）成分可作为CAA的诊断生物标志物。我们研究了肽 A beta 38、A beta 40、A beta 42 和 A beta 43 对散发性 CAA (sCAA)、遗传性荷兰型 CAA (D-CAA) 和阿尔茨海默病 (AD) 患者的诊断潜力。方法：在发现组（26 名 sCAA 患者和 40 名对照患者）和验证组（40 名患有 sCAA 的患者）中通过免疫分析对 A β 肽进行定量。 sCAA，40 名 AD 患者和 37 名对照），以及一组 22 名 D-CAA 患者和 54 名对照。为了确定诊断准确性，使用置信区间 (CI) 为 95% 的受试者工作特征曲线计算曲线下面积 (AUC)。 结果：我们发现与对照组相比，sCAA 患者和 D-CAA 患者的所有 A β 肽水平均降低。 A beta 42（sCAA 与对照的 AUC 发现：0.90，95% CI = 0.82-0.99；验证：0.94，95% CI = 0.89-0.99）和 A beta 43（sCAA 与对照的 AUC 发现：0.95，95% CI = 0.88-1.00；对于验证：0.91，95% CI = 0.83-1.0）。与 AD 相比，sCAA 中除 Aβ 43 外的所有 A β 肽均减少（CSFA β 38：AUC = 0.82，95% CI = 0.71-0.93；CSFA β 40：AUC = 0.88，95% CI = 0.80-0.96；CSFA β 42：AUC = 0.79，95% CI = 0.79，95% CI = 0.66-0.92).解释：CSF A beta 38、A beta 40、A beta 42 和 A beta 43 的组合生物标志物组有可能区分 sCAA 与 AD 和对照，以及 D-CAA 与对照。安神经学 2023
Objective: Vascular amyloid beta (A beta) 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 A beta 38, A beta 40, A beta 42, and A beta 43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).Methods: A beta 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 A beta peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for A beta 42 (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 A beta 43 (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 A beta peptides except A beta 43 were also decreased in sCAA compared to AD (CSF A beta 38: AUC = 0.82, 95% CI = 0.71-0.93; CSF A beta 40: AUC = 0.88, 95% CI = 0.80-0.96; CSF A beta 42: AUC = 0.79, 95% CI = 0.66-0.92).Interpretation: A combined biomarker panel of CSF A beta 38, A beta 40, A beta 42, and A beta 43 has potential to differentiate sCAA from AD and controls, and D-CAA from controls. ANN NEUROL 2023