APPswe/PS1δE9 mice exhibit low oxygen saturation and alterations of erythrocytes preceding the neuropathology and cognitive deficiency during Alzheimer's disease

Aim: The molecular mechanism underlying Alzheimer's disease (AD) pathologies remains unclear. The brain is extremely sensitive to oxygen deprivation, and brief interruptions in oxygen supply may lead to permanent brain damage. The objective here was to access the red blood cell (RBC) physiological alterations and the changes in blood oxygen saturation of an AD model as well as to explore the possible mechanism underlying these pathologies.Methods: We used female APP(swe)/PS1(delta E9) mice as AD models. Data were collected at the age of 3, 6, and 9 months. In addition to examining classic features of AD, namely cognitive deficiency and A beta depositions, 24 h blood oxygen saturation was monitored by Plus oximeters in real time. In addition, RBC physiological parameters were measured by blood cell counter using peripheral blood from the epicanthal veins. Furthermore, in the mechanism investigations, the expression of phosphorylated band 3 protein was examined by a series of Western blot analyses, and the levels of soluble A beta 40 and A beta 42 on the membrane of RBCs were determined by ELISA.Results: Our results showed that the blood oxygen saturation in the AD mice was significantly reduced as early as at 3 months of age, preceding the neuropathological changes and cognitive impairments. Meanwhile, the expression of phosphorylated band 3 protein and levels of soluble A beta 40 and A beta 42 were all elevated in the erythrocytes of the AD mice.Conclusion: APP(swe)/PS1(delta E9) mice exhibited decreased oxygen saturation together with reduced RBC counts and hemoglobin concentrations at the early stage, which may aid in the development of predictive markers for AD diagnosis. The increased expression of band 3 protein and elevated A beta 40 and A beta 42 levels may contribute to the deformation of RBCs and, in turn, cause the subsequent AD development.

Automated summary

The aim of this study was to explore the molecular mechanism underlying Alzheimer's disease (AD) pathologies. The results showed that blood oxygen saturation in AD mice was significantly reduced in the early stages, along with decreased red blood cell counts and hemoglobin concentrations, which may contribute to the development of predictive markers for AD diagnosis. Furthermore, increased expression of band 3 protein and elevated levels of soluble Aβ40 and Aβ42 may cause deformation of red blood cells and subsequent AD development.