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阿尔茨海默病病理学与 TgF344-AD 大鼠健康衰老相比,与血脑屏障水通透性的早期改变有关。

Alzheimer's disease pathology is associated with earlier alterations to blood-brain barrier water permeability compared with healthy ageing in TgF344-AD rats.

机构信息

Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine, and Health, Stopford Building, University of Manchester, Manchester, UK.

Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Manchester, UK.

出版信息

NMR Biomed. 2021 Jul;34(7):e4510. doi: 10.1002/nbm.4510. Epub 2021 Mar 15.

Abstract

The effects of Alzheimer's disease (AD) and ageing on blood-brain barrier (BBB) breakdown are investigated in TgF344-AD and wild-type rats aged 13, 18 and 21 months. Permeability surface area products of the BBB to water (PS ) and gadolinium-based contrast agent (PS ) were measured in grey matter using multiflip angle multiecho dynamic contrast-enhanced MRI. At 13 months of age, there was no significant difference in PS between TgF344-AD and wild-types (p = 0.82). Between 13 and 18 months, PS increased in TgF344-AD rats (p = 0.027), but not in wild-types (p = 0.99), leading to significantly higher PS in TgF344-AD rats at 18 months, as previously reported (p = 0.012). Between 18 and 21 months, PS values increased in wild-types (p = 0.050), but not in TgF344-AD rats (p = 0.50). These results indicate that BBB water permeability is affected by both AD pathology and ageing, but that changes occur earlier in the presence of AD pathology. There were no significant genotype or ageing effects on PS (p > 0.05). In conclusion, we detected increases in BBB water permeability with age in TgF344-AD and wild-type rats, and found that changes occurred at an earlier age in rats with AD pathology.

摘要

阿尔茨海默病(AD)和衰老对血脑屏障(BBB)破坏的影响在 13、18 和 21 个月大的 TgF344-AD 和野生型大鼠中进行了研究。使用多翻转角多回波动态对比增强 MRI 在灰质中测量 BBB 对水(PS )和基于钆的对比剂(PS )的通透性表面积产物。在 13 个月大时,TgF344-AD 和野生型之间 PS 没有显著差异(p = 0.82)。在 13 至 18 个月之间,TgF344-AD 大鼠的 PS 增加(p = 0.027),而野生型大鼠则没有(p = 0.99),导致 18 个月时 TgF344-AD 大鼠的 PS 显著升高,如前所述(p = 0.012)。在 18 至 21 个月之间,野生型大鼠的 PS 值增加(p = 0.050),而 TgF344-AD 大鼠则没有(p = 0.50)。这些结果表明,BBB 水通透性受 AD 病理学和衰老的影响,但在存在 AD 病理学的情况下,变化发生得更早。PS 没有明显的基因型或衰老影响(p > 0.05)。总之,我们在 TgF344-AD 和野生型大鼠中检测到 BBB 水通透性随年龄增长而增加,并发现 AD 病理大鼠的变化发生在更早的年龄。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ef0/11475392/2808abd113cb/NBM-34-e4510-g005.jpg

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