Associations Between Plasma Klotho with Renal Function and Cerebrospinal Fluid Amyloid-β Levels in Alzheimer’s Disease: The Chongqing Ageing & Dementia Study

Article type: Research Article

Authors: Ren, Jun-Rong^{a; b; c} | Wang, Zhen^d | Cheng, Yuan^{a; b; c} | He, Chen-Yang^{a; b; c} | Jian, Jie-Ming^{a; b; c} | Fan, Dong-Yu^{a; b; c} | Shen, Ying-Ying^{a; b; c} | Chen, Dong-Wan^{a; b; c} | Li, Hui-Yun^{a; b; c} | Yi, Xu^{a; b; c} | Zeng, Gui-Hua^{a; b; c} | Tan, Cheng-Rong^{a; b; c} | Shi, An-Yu^{a; b; c} | Chen, Li-Yong^e | Mao, Qing-Xiang^e | Wang, Yan-Jiang^{a; b; c; f; g; h; *} | Wang, Jun^{a; b; c; *}

Affiliations: [a] Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China | [b] Institute of Brain and Intelligence, Third Military Medical University, Chongqing, China | [c] Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China | [d] Department of Critical Care Medicine, Daping Hospital, Third Military Medical University, Chongqing, China | [e] Department of Anaesthesiology, Daping Hospital, Third Military Medical University, Chongqing, China | [f] Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, China | [g] Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China | [h] State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, China

Correspondence: [*] Correspondence to: Yan-Jiang Wang and Jun Wang, Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China. E-mail: yanjiang_wang@tmmu.edu.cn and qywangjun@163.com.

Abstract: Background:The kidney-brain crosstalk has been involved in Alzheimer’s disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. Objective:To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. Methods:We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-β (Aβ)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aβ, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Results:We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aβ42, Aβ40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aβ42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aβ42. Conclusion:Renal function impacts brain Aβ metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD.

Keywords: Alzheimer’s disease, amyloid-β, estimated glomerular filtration rate, kidney-brain crosstalk, Klotho

DOI: 10.3233/JAD-221107

Journal: Journal of Alzheimer's Disease, vol. 92, no. 2, pp. 477-485, 2023