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

doi:10.3389/fnmol.2021.723317

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

Front Mol Neurosci. 2021 Aug 27:14:723317. doi: 10.3389/fnmol.2021.723317. eCollection 2021.

Authors

Liding Zhang^{1

2}, Changwen Yang^{1

2}, Yanqing Li^{1

2}, Shiqi Niu^{1

2}, Xiaohan Liang^{1

2}, Zhihong Zhang^{1

2

3}, Qingming Luo^{1

2

3}, Haiming Luo^{1

2}

Affiliations

¹ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.
² MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China.
³ School of Biomedical Engineering, Hainan University, Haikou, China.

Abstract

Although amyloid-β₄₂ (Aβ₄₂) 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 Aβ₄₂-specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect Aβ₄₂ types using sandwich ELISA, including total Aβ₄₂, Aβ₄₂ oligomers (Aβ₄₂Os), and Aβ₄₂ monomers (Aβ₄₂Ms). The levels of Aβ₄₂ species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total Aβ₄₂ levels in the blood were not correlated with AD progression, but Aβ₄₂Ms level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and Aβ₄₂Os level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of Aβ₄₂Ms and Aβ₄₂Os in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of Aβ₄₂ in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of Aβ₄₂ 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.

Keywords: Alzheimer’s disease; ELISA – enzyme-linked immunosorbent assay; blood Aβ42; dynamic distribution; intestinal Aβ.