Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease
Liding Zhang, Changwen Yang, Yanqing Li, Shiqi Niu, Xiaohan Liang, Zhihong Zhang, Qingming Luo, Haiming Luo
Abstract
Although amyloid-β 42 (Aβ 42 ) has been used as one of the core biomarkers for Alzheimer’s disease (AD) diagnosis, the dynamic changes of its different forms in the brain, blood, and even intestines and its correlation with the progression of AD disease remain obscure. Herein, we screened Aβ 42 -specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect Aβ 42 types using sandwich ELISA, including total Aβ 42 , Aβ 42 oligomers (Aβ 42 Os), and Aβ 42 monomers (Aβ 42 Ms). The levels of Aβ 42 species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total Aβ 42 levels in the blood were not correlated with AD progression, but Aβ 42 Ms level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and Aβ 42 Os level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of Aβ 42 Ms and Aβ 42 Os in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of Aβ 42 in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of Aβ 42 in the gastrointestinal organs may also be related to the progression of AD. Meanwhile, changes in the gut microbiota composition of APP/PS1 mice with age were also observed. Therefore, the increase in Aβ derived from intestinal tissues and changes in microbiome composition can be used as a potential early diagnosis tool for AD, and further used as an indicator of drug intervention to reduce brain amyloid.