Serum Uric Acid May Aggravate Alzheimer’s Disease Risk by Affecting Amyloidosis in Cognitively Intact Older Adults: The CABLE Study

Article type: Research Article

Authors: Li, Lin-Lin^{a; 1} | Ma, Ya-Hui^{b; 1} | Bi, Yan-Lin^{c; 1} | Sun, Fu-Rong^b | Hu, Hao^b | Hou, Xiao-He^b | Xu, Wei^b | Shen, Xue-Ning^d | Dong, Qiang^d | Tan, Lan^{a; b; *} | Yang, Jiu-Long^{e; *} | Yu, Jin-Tai^{d; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [c] Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China | [d] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China | [e] Qingdao Municipal Hospital, Qingdao University, Qingdao, China

Correspondence: [*] Correspondence to: Jin-Tai Yu, MD, PhD, Huashan Hospital, Fudan University, No. 12 Wulumuqi Road, Shanghai, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: yu-jintai@163.com; Lan Tan, MD, PhD, or Prof. Jiu-Long Yang, Qingdao Municipal Hospital, Qingdao University, No.5 Donghai Middle Road, Qingdao, China. E-mails: dr.tanlan@163.com (L. Tan); and waj2002@126.com (J.L. Yang).

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

Abstract: Background:Serum uric acid (SUA) affects the reaction of oxidative stress and free radicals in the neurodegenerative processes. However, whether SUA impacts Alzheimer’s disease (AD) pathology remains unclear. Objective:We aimed to explore whether high SUA levels can aggravate the neurobiological changes of AD in preclinical AD. Methods:We analyzed cognitively intact participants (n = 839, age 62.16 years) who received SUA and cerebrospinal fluid (CSF) biomarkers (amyloid-β [Aβ], total tau [t-Tau], and phosphorylated tau [p-Tau]) measurements from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database using multivariable-adjusted linear models. Results:Levels of SUA in the preclinical AD elevated compared with the healthy controls (p = 0.007) and subjects with amyloid pathology had higher concentration of SUA than controls (p = 0.017). Roughly, equivalent levels of SUA displayed among cognitively intact individuals with or without tau pathology and neurodegeneration. CSF Aβ1 - 42 (p = 0.019) and Aβ1 - 42/Aβ1 - 40 (p = 0.027) were decreased and CSF p-Tau/Aβ1 - 42 (p = 0.009) and t-Tau/Aβ1 - 42 (p = 0.043) were increased with the highest (> 75th percentile) SUA when compared to lowest SUA, implying a high burden of cerebral amyloidosis in individuals with high SUA. Sensitivity analyses using the usual threshold to define hyperuricemia and precluding drug effects yielded robust associations. Nevertheless, the quadratic model did not show any U-shaped relationships between them. Conclusion:SUA may aggravate brain amyloid deposition in preclinical AD, which corroborated the detrimental role of SUA.

Keywords: Alzheimer’s disease pathology, biomarkers, cerebrospinal fluid, serum uric acid

DOI: 10.3233/JAD-201192

Journal: Journal of Alzheimer's Disease, vol. 81, no. 1, pp. 389-401, 2021