医学
脑淀粉样血管病
脑脊液
异常
血管病
高强度
淀粉样蛋白(真菌学)
生物标志物
病理
病态的
白质
磁共振成像
内科学
疾病
痴呆
放射科
内分泌学
糖尿病
生物化学
化学
精神科
作者
Emma A. Koemans,Ingeborg Rasing,Sabine Voigt,Thijs W. van Harten,Reinier G.J. van der Zwet,Kanishk Kaushik,M. Schipper,Nelleke van der Weerd,Erik W. van Zwet,Ellis S. van Etten,Matthias J.P. van Osch,H. Bea Kuiperij,Marcel M. Verbeek,Gisela M. Terwindt,Steven M. Greenberg,Marianne A.A. van Walderveen,Marieke J.H. Wermer
出处
期刊:Stroke
[Ovid Technologies (Wolters Kluwer)]
日期:2024-04-01
卷期号:55 (4): 954-962
标识
DOI:10.1161/strokeaha.123.044688
摘要
The temporal ordering of biomarkers for cerebral amyloid angiopathy (CAA) is important for their use in trials and for the understanding of the pathological cascade of CAA. We investigated the presence and abnormality of the most common biomarkers in the largest (pre)symptomatic Dutch-type hereditary CAA (D-CAA) cohort to date.We included cross-sectional data from participants with (pre)symptomatic D-CAA and controls without CAA. We investigated CAA-related cerebral small vessel disease markers on 3T-MRI, cerebrovascular reactivity with functional 7T-MRI (fMRI) and amyloid-β40 and amyloid-β42 levels in cerebrospinal fluid. We calculated frequencies and plotted biomarker abnormality according to age to form scatterplots.We included 68 participants with D-CAA (59% presymptomatic, mean age, 50 [range, 26-75] years; 53% women), 53 controls (mean age, 51 years; 42% women) for cerebrospinal fluid analysis and 36 controls (mean age, 53 years; 100% women) for fMRI analysis. Decreased cerebrospinal fluid amyloid-β40 and amyloid-β42 levels were the earliest biomarkers present: all D-CAA participants had lower levels of amyloid-β40 and amyloid-β42 compared with controls (youngest participant 30 years). Markers of nonhemorrhagic injury (>20 enlarged perivascular spaces in the centrum semiovale and white matter hyperintensities Fazekas score, ≥2, present in 83% [n=54]) and markers of impaired cerebrovascular reactivity (abnormal BOLD amplitude, time to peak and time to baseline, present in 56% [n=38]) were present from the age of 30 years. Finally, markers of hemorrhagic injury were present in 64% (n=41) and only appeared after the age of 41 years (first microbleeds and macrobleeds followed by cortical superficial siderosis).Our results suggest that amyloid biomarkers in cerebrospinal fluid are the first to become abnormal in CAA, followed by MRI biomarkers for cerebrovascular reactivity and nonhemorrhagic injury and lastly hemorrhagic injury. This temporal ordering probably reflects the pathological stages of CAA and should be taken into account when future therapeutic trials targeting specific stages are designed.
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