Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
Elife. 2021 Feb 12;10:e61279. doi: 10.7554/eLife.61279.
Impaired cerebrovascular function is an early biomarker for cerebral amyloid angiopathy (CAA), a neurovascular disease characterized by amyloid-β accumulation in the cerebral vasculature, leading to stroke and dementia. The transgenic Swedish Dutch Iowa (Tg-SwDI) mouse model develops cerebral microvascular amyloid-β deposits, but whether this leads to similar functional impairments is incompletely understood. We assessed cerebrovascular function longitudinally in Tg-SwDI mice with arterial spin labeling (ASL)-magnetic resonance imaging (MRI) and laser Doppler flowmetry (LDF) over the course of amyloid-β deposition. Unexpectedly, Tg-SwDI mice showed similar baseline perfusion and cerebrovascular reactivity estimates as age-matched wild-type control mice, irrespective of modality (ASL or LDF) or anesthesia (isoflurane or urethane and α-chloralose). Hemodynamic changes were, however, observed as an effect of age and anesthesia. Our findings contradict earlier results obtained in the same model and question to what extent microvascular amyloidosis as seen in Tg-SwDI mice is representative of cerebrovascular dysfunction observed in CAA patients.
脑血管功能障碍是脑淀粉样血管病（CAA）的早期生物标志物，CAA 是一种以脑血管中淀粉样β积累为特征的神经血管疾病，可导致中风和痴呆。转基因瑞典荷兰爱荷华州（Tg-SwDI）小鼠模型会产生脑微血管淀粉样β沉积物，但这是否会导致类似的功能障碍尚不完全清楚。我们通过动脉自旋标记（ASL）-磁共振成像（MRI）和激光多普勒流量测定（LDF），在淀粉样β沉积过程中对 Tg-SwDI 小鼠进行了脑血管功能的纵向评估。出乎意料的是，无论模态（ASL 或 LDF）或麻醉（异氟烷或乌拉坦和α-氯醛）如何，Tg-SwDI 小鼠的基线灌注和脑血管反应性估计值与同龄野生型对照小鼠相似。然而，随着年龄和麻醉的变化，观察到了血液动力学的变化。我们的研究结果与在同一模型中获得的早期结果相矛盾，并质疑 Tg-SwDI 小鼠中所见的微血管淀粉样变性在多大程度上代表了 CAA 患者中观察到的脑血管功能障碍。
