Vascular perturbations and cerebral hypometabolism are emerging as important components of Alzheimer's disease (AD). While various in vivo imaging modalities have been designed to detect changes of cerebral perfusion and metabolism in AD patients and animal models, study results were often heterogenous with respect to imaging techniques and animal models. We therefore evaluated cerebral perfusion and glucose metabolism of two popular transgenic AD mouse strains, TgCRND8 and 5xFAD, at 7 and 12 months-of-age under identical conditions and analyzed possible molecular mechanisms underlying heterogeneous cerebrovascular phenotypes. Results revealed disparate findings in these two strains, displaying important aspects of AD progression. TgCRND8 mice showed significantly decreased cerebral blood flow and glucose metabolism with unchanged cerebral blood volume (CBV) at 12 months-of-age whereas 5xFAD mice showed unaltered glucose metabolism with significant increase in CBV at 12 months-of-age and a biphasic pattern of early hypoperfusion followed by a rebound to normal cerebral blood flow in late disease. Finally, immunoblotting assays suggested that VEGF dependent vascular tone change may restore normoperfusion and increase CBV in 5xFAD.

血管紊乱和脑代谢低下正在成为阿尔茨海默病 (AD) 的重要组成部分。虽然已经设计了各种体内成像方式来检测 AD 患者和动物模型中脑灌注和代谢的变化，但成像技术和动物模型的研究结果往往是异质的。因此，我们在相同条件下评估了两种流行的转基因 AD 小鼠品系 TgCRND8 和 5xFAD 在 7 月龄和 12 月龄时的脑灌注和葡萄糖代谢，并分析了异质脑血管表型背后的可能分子机制。结果揭示了这两种菌株的不同发现，显示了 AD 进展的重要方面。TgCRND8 小鼠在 12 月龄时表现出脑血流量和葡萄糖代谢显着降低，而脑血容量 (CBV) 不变，而 5xFAD 小鼠则表现出葡萄糖代谢未改变，在 12 月龄时 CBV 显着增加，并且出现双相模式早期低灌注，随后在疾病晚期反弹至正常脑血流量。最后，免疫印迹分析表明，VEGF 依赖性血管张力变化可能会恢复正常灌注并增加 5xFAD 中的 CBV。