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

Autor: Jun-Rong Ren, Zhen Wang, Yuan Cheng, Chen-Yang He, Jie-Ming Jian, Dong-Yu Fan, Ying-Ying Shen, Dong-Wan Chen, Hui-Yun Li, Xu Yi, Gui-Hua Zeng, Cheng-Rong Tan, An-Yu Shi, Li-Yong Chen, Qing-Xiang Mao, Yan-Jiang Wang, Jun Wang
Rok vydání: 2023
Předmět:
Zdroj: Journal of Alzheimer's Disease. 92:477-485
ISSN: 1875-8908
1387-2877
Popis: 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.
Databáze: OpenAIRE