Increase of BACE1, Brain-Renal Risk Factor, Contributes to Kidney Damage in an Alzheimer’s Disease Mouse Model

Article type: Research Article

Authors: Shi, Yan^{a; b; 1} | Gao, Feng^{c; d; 1} | Yang, Xiaoli^{c; d} | Liu, Dongwei^b | Han, Qiuxia^{a; b} | Liu, Zhangsuo^{b; *} | Zhu, Hanyu^{a; *} | Shen, Yong^{c; d}

Affiliations: [a] Department of Nephrology, the First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, China | [b] Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University, Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, China | [c] Institute on Aging and Brain Disorders, First Affiliated Hospital of University of Science and Technology of China, Hefei, China | [d] Neurodegenerative Disorder Research Center, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

Correspondence: [*] Correspondence to: Hanyu Zhu, Department of Nephrology, the First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, China. Tel.: +86 010 66937763; E-mail: [email protected]; Zhangsuo Liu, Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University, Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, China. Tel.: +86 0371 66295921; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:It is believed that there is a certain correlation between the brain and kidneys, but it is poorly understood. Many findings suggested that there were previously unknown signaling pathways involving AβPP and BACE1 in the kidney. Objective:Exploring the changes of BACE1 activity in APP23 mouse kidneys, providing evidence for the function of AβPP and BACE1 activity in the kidney. Methods:The activity and expression of BACE1 were detected in the kidney of APP23 mice by enzymatic assay and western blotting. The protein expression levels of AβPP, claudin1, occludin, VE-cadherin, and Klotho (membrane-form klotho) were examined by using western blotting. The renal pathological changes of APP23 mice were examined by the routine renal pathological procedures. Results:In this study, we found that the AβPP protein level was increased in kidneys of APP23 mice compared with wild-type (WT) mice. Additionally, the activity and expression of BACE1 were increased in kidneys of APP23 mice compared to that of WT. BACE1 was predominantly distributed on the lumen side of renal tubular epithelial cells. The protein levels of Klotho and VE-cadherin were decreased, occludin expression was also decreased, and claudin-1 expression was increased. Renal pathological damage which observed in kidneys of APP23 mice was more serious than that in kidneys of WT mice. Conclusion:Our findings suggest that the increase of AβPP protein levels under Thy-1 neuron promoter in the APP23 mice promoted the increase of renal BACE1 expression and enzymatic activity in the kidneys. Moreover, certain pathological damage in the kidneys of APP23 mice were observed. APP23 mice are easily affected by external risk factors compared with WT mice.

Keywords: Alzheimer’s disease, APP23, BACE1, brain-renal risk factor, kidney

DOI: 10.3233/JAD-200204

Journal: Journal of Alzheimer's Disease, vol. 76, no. 1, pp. 237-248, 2020