TY - JOUR
T1 - APPswe/PS1ΔE9 mice exhibit low oxygen saturation and alterations of erythrocytes preceding the neuropathology and cognitive deficiency during Alzheimer's disease
AU - Wang, Manli
AU - Chen, Xi
AU - Niu, Long
AU - Xu, Jianli
AU - Yu, Hang
AU - Xu, Xiaojiao
AU - Yang, Qiu
AU - Xiang, Yang
AU - Le, Weidong
N1 - Funding Information:
University Innovative Research Fund of China (ZYGX2020ZB035 to LWD), The youth program of National Natural Science Foundation of China (81901405 to CX), the Key research and development program of Sichuan (2021YFS0382 to CX).
Publisher Copyright:
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
PY - 2023/7
Y1 - 2023/7
N2 - 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 APPswe/PS1ΔE9 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 Aβ 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 Aβ40 and Aβ42 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 Aβ40 and Aβ42 were all elevated in the erythrocytes of the AD mice. Conclusion: APPswe/PS1ΔE9 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 Aβ40 and Aβ42 levels may contribute to the deformation of RBCs and, in turn, cause the subsequent AD development.
AB - 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 APPswe/PS1ΔE9 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 Aβ 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 Aβ40 and Aβ42 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 Aβ40 and Aβ42 were all elevated in the erythrocytes of the AD mice. Conclusion: APPswe/PS1ΔE9 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 Aβ40 and Aβ42 levels may contribute to the deformation of RBCs and, in turn, cause the subsequent AD development.
KW - Alzheimer's disease
KW - oxygen deficiency
KW - oxygen saturation
KW - red blood cells
KW - Oxygen
KW - Erythrocytes/pathology
KW - Mice, Transgenic
KW - Cognition
KW - Presenilin-1/genetics
KW - Animals
KW - Amyloid beta-Protein Precursor/genetics
KW - Anion Exchange Protein 1, Erythrocyte/metabolism
KW - Female
KW - Mice
KW - Oxygen Saturation
KW - Alzheimer Disease/metabolism
KW - Amyloid beta-Peptides/metabolism
KW - Disease Models, Animal
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U2 - 10.1111/cns.14147
DO - 10.1111/cns.14147
M3 - Article
C2 - 36883266
AN - SCOPUS:85150448703
SN - 1755-5930
VL - 29
SP - 1889
EP - 1897
JO - CNS Neuroscience and Therapeutics
JF - CNS Neuroscience and Therapeutics
IS - 7
ER -