Association between serum urate and CSF markers of Alzheimer's disease pathology in a population-based sample of 70-year-olds

Introduction: The relationship between urate and biomarkers for Alzheimer's disease (AD) pathophysiology has not been investigated. Methods: We examined whether serum concentration of urate was associated with cerebrospinal fluid biomarkers, amyloid beta (Aβ)₄₂, Aβ₄₀, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), and Aβ₄₂/Aβ₄₀ ratio, in cognitively unimpaired 70-year-old individuals from Gothenburg, Sweden. We also evaluated whether possible associations were modulated by the apolipoprotein E (APOE) ε4 allele. Results: Serum urate was positively associated with Aβ₄₂ in males (β = 0.55 pg/mL, P =.04). There was a positive urate–APOE ε4 interaction (1.24 pg/mL, P_interaction =.02) in relation to Aβ₄₂ association. The positive urate and Aβ₄₂ association strengthened in male APOE ε4 carriers (β = 1.28 pg/mL, P =.01). Discussion: The positive association between urate and Aβ₄₂ in cognitively healthy men may suggest a protective effect of urate against deposition of amyloid protein in the brain parenchyma, and in the longer term, maybe against AD dementia.