Alten Baris, Gokcal Elif, Warren Andrew, van Veluw Susanne J, Kozberg Mariel, Gurol M Edip, Viswanathan Anand, Greenberg Steven M
Mass General Brigham Neurology Residency Program Boston MA USA.
Department of Neurology Massachusetts General Hospital Boston MA USA.
J Am Heart Assoc. 2025 Mar 4;14(5):e040025. doi: 10.1161/JAHA.124.040025. Epub 2025 Mar 3.
Cerebral amyloid angiopathy (CAA) is driven by vascular Aβ (amyloid-beta) deposition, which can be detected as reduced Aβ species in cerebrospinal fluid (CSF). We sought to identify relationships between CSF Aβ and tau concentrations and various manifestations of CAA.
This is a retrospective cross-sectional single-center study of patients diagnosed with CAA per Boston Criteria version 2.0, had magnetic resonance imaging brain scans, and underwent CSF testing for Aβ and tau concentrations between 2008 and 2022. Associations between clinical/magnetic resonance imaging features and CSF biomarker concentrations were investigated with univariate and multivariate models.
We identified 31 patients aged 69.6±8.4 years, of whom 20 presented with cognitive complaints, 9 with CAA-related macrohemorrhage (lobar intraparenchymal or convexity subarachnoid hemorrhage), and 2 with transient focal neurological episodes. Presence of macrohemorrhage (301.8±112 pg/mL versus 400.9±123 pg/mL, =0.029), cortical superficial siderosis (309.6±131 mg/dL versus 412.3±100 pg/mL, =0.021), and severe enlarged perivascular spaces in centrum semiovale (285.8±91 pg/mL versus 428.3±117 pg/mL, <0.001) were associated with lower Aβ42 concentrations. Aβ42 concentrations inversely correlated with the number of these manifestations, being lowest in patients having all three. Patients with cognitive complaints had higher t-tau (total tau; 551±320 pg/mL versus 317.2±141 pg/mL, =0.03) and trended toward having higher p-tau (phosphorylated tau at threonine 181) concentrations (75.69±39 pg/mL versus 49.24±22 pg/mL, =0.05).
Lower CSF Aβ42, suggesting higher amyloid burden, is associated with CAA-related macrohemorrhages and severe enlarged perivascular spaces in centrum semiovale, suggesting potential mechanistic links and CSF Aβ42 as a potential biomarker for progression of CAA. CSF tau concentrations are linked to cognitive complaints, likely representing comorbid Alzheimer disease pathology.
脑淀粉样血管病（CAA）由血管β淀粉样蛋白（Aβ）沉积驱动，这可在脑脊液（CSF）中检测为Aβ种类减少。我们试图确定脑脊液Aβ和tau浓度与CAA的各种表现之间的关系。
这是一项回顾性横断面单中心研究，研究对象为根据波士顿标准2.0版诊断为CAA、进行了脑部磁共振成像扫描并在2008年至2022年期间接受了脑脊液Aβ和tau浓度检测的患者。使用单变量和多变量模型研究临床/磁共振成像特征与脑脊液生物标志物浓度之间的关联。
我们确定了31例年龄为69.6±8.4岁的患者，其中20例有认知主诉，9例有CAA相关的大出血（脑叶实质内或脑凸面蛛网膜下腔出血），2例有短暂性局灶性神经发作。大出血的存在（301.8±112 pg/mL对400.9±123 pg/mL，P = 0.029）、皮质表面铁沉积（309.6±131 mg/dL对412.3±100 pg/mL，P = 0.021）以及半卵圆中心严重扩大的血管周围间隙（285.8±91 pg/mL对428.3±117 pg/mL，P<0.001）与较低的Aβ42浓度相关。Aβ42浓度与这些表现的数量呈负相关，在具有所有三种表现的患者中最低。有认知主诉的患者总tau（t-tau）水平较高（551±320 pg/mL对317.2±141 pg/mL，P = 0.03），且磷酸化tau（苏氨酸181位点的磷酸化tau，p-tau）浓度有升高趋势（75.69±39 pg/mL对49.24±22 pg/mL，P = 0.05）。
脑脊液Aβ42降低表明淀粉样蛋白负荷较高，与CAA相关的大出血和半卵圆中心严重扩大的血管周围间隙相关，提示潜在的机制联系以及脑脊液Aβ42作为CAA进展的潜在生物标志物。脑脊液tau浓度与认知主诉有关，可能代表合并的阿尔茨海默病病理。
