Dynamic Changes in the Levels of Amyloid-beta(42) Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer's Disease

Although amyloid-beta(42) (A beta(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 A beta(42)-specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect A beta(42) types using sandwich ELISA, including total A beta(42), A beta(42) oligomers (A beta Os-42), and A beta(42) monomers (A beta Ms-42). The levels of A beta(42) species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total A beta(42) levels in the blood were not correlated with AD progression, but A beta Ms-42 level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and A beta Os-42 level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of A beta Ms-42 and A beta Os-42 in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of A beta(42) in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of A beta(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 A beta 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.