Department of Pharmacy, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, South Korea.
Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon, 21983, South Korea.
Adv Sci (Weinh). 2022 Apr;9(12):e2104542. doi: 10.1002/advs.202104542. Epub 2022 Feb 2.
Amyloid-β (Aβ) deposition in the brain is a primary biomarker of Alzheimer's disease (AD) and Aβ measurement for AD diagnosis mostly depends on brain imaging and cerebrospinal fluid analyses. Blood Aβ can become a reliable surrogate biomarker if issues of low concentration for conventional laboratory instruments and uncertain correlation with brain Aβ are solved. Here, brain-to-blood efflux of Aβ is stimulated in AD transgenic mice by orally administrating a chemical that dissociates amyloid plaques and observing the subsequent increase of blood Aβ concentration. 5XFAD transgenic and wild-type mice of varying ages and genders are prepared, and blood samples of each mouse are collected six times for 12 weeks; three weeks of no treatment and additional nine weeks of daily oral administration, ad libitum, of Aβ plaque-dissociating chemical agent. By the dissociation of Aβ aggregates, the altered levels of plasma Aβ distinguish between transgenic and wild-type mice, displaying potential as an amyloid burden marker of AD brains.
脑内淀粉样蛋白-β(Aβ)沉积是阿尔茨海默病(AD)的主要生物标志物,Aβ的测量主要依赖于脑成像和脑脊液分析。如果能够解决常规实验室仪器浓度低的问题,并且与脑 Aβ的相关性不确定的问题,那么血液 Aβ可以成为可靠的替代生物标志物。在这里,通过口服给予一种能够使淀粉样斑块解离的化学物质来刺激 AD 转基因小鼠脑内 Aβ外排,观察随后血液 Aβ浓度的增加。制备了不同年龄和性别的 5XFAD 转基因和野生型小鼠,并在 12 周内对每只小鼠采集 6 次血样;3 周不治疗,然后每天自由口服 Aβ斑块解离化学试剂 9 周。通过 Aβ 聚集体的解离,改变的血浆 Aβ水平能够区分转基因和野生型小鼠,显示出作为 AD 大脑淀粉样蛋白负担标志物的潜力。