Margraf Nils G, Jensen-Kondering Ulf, Weiler Caroline, Leypoldt Frank, Maetzler Walter, Philippen Sarah, Bartsch Thorsten, Flüh Charlotte, Röcken Christoph, Möller Bettina, Royl Georg, Neumann Alexander, Brüggemann Norbert, Roeben Benjamin, Schulte Claudia, Bender Benjamin, Berg Daniela, Kuhlenbäumer Gregor
Department of Neurology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University, Kiel, Germany.
Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University, Kiel, Germany.
Front Aging Neurosci. 2022 Feb 14;14:783996. doi: 10.3389/fnagi.2022.783996. eCollection 2022.
To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort.
Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.
In our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau (AUC 0.71). P-tau (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis.
The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.
在一项回顾性多中心队列研究中，根据改良波士顿标准评估脑脊液（CSF）生物标志物对可能患有脑淀粉样血管病（CAA）患者的诊断准确性。
检测了31例可能患有CAA的患者、28例阿尔茨海默病（AD）患者和30例对照者的β-淀粉样蛋白1-40（Aβ40）、β-淀粉样蛋白1-42（Aβ42）、总tau蛋白（t-tau）和磷酸化tau蛋白181（p-tau）。对测量参数以及Aβ42/40比值进行受试者操作特征（ROC）分析以估计诊断参数。对所有合适的已发表研究进行了荟萃分析。
在我们的数据中，Aβ42/40（曲线下面积[AUC]为0.88）在区分CAA和对照方面表现最佳，而Aβ40表现不佳（AUC为0.63）。在区分CAA和AD时，本研究中p-tau（AUC为0.75）区分效果最佳，而Aβ40（AUC为0.58）和Aβ42（AUC为0.54）无区分能力。在荟萃分析中，Aβ42/40（AUC为0.90）在区分CAA和对照方面表现最佳，其次是t-tau（AUC为0.79）、Aβ40（AUC为0.76）和p-tau（AUC为0.71）。p-tau（AUC为0.76）、Aβ40（AUC为0.73）和t-tau（AUC为0.71）在区分AD和CAA方面表现相当，而Aβ42（AUC为0.54）则不然。与研究AD生物标志物的研究一致，本研究以及荟萃分析中Aβ42/40在区分AD和对照方面表现出色（AUC为0.92 - 0.96）。
所分析的参数在区分对照和CAA方面具有临床有用的准确性（AUC > ∼0.85），但在区分CAA和AD方面则不然。由于CAA和AD之间存在神经病理学、临床和诊断的连续性，其他诊断标志物，例如新型CSF生物标志物或其他参数可能会更成功。
