Effects of Probucol on plasma amyloid-β transport in patients with hyperlipidemia: a 12-week randomized, double-blind, placebo-controlled trial

BackgroundAlthough dyslipidemia has been acknowledged as a risk factor for Alzheimer's disease (AD), the effects of lipid-lowering drugs on AD have not been determined. The primary pathophysiological hallmark of AD is the deposition of amyloid-beta (A beta) plaques in the brain. Plasma A beta levels are influenced by the transport of A beta from the central nervous system to the peripheral blood. This study investigates the effects of Probucol, a lipid-lowering and antioxidant drug, on plasma A beta transport.MethodsA total of 120 hyperlipidemic patients with normal cognition were randomly assigned (1:1 ratio) to receive either Probucol (1000 mg daily for 12 weeks) or a placebo. Plasma A beta, soluble receptor of advanced glycation end products (sRAGE), and fasting lipid profiles were measured at baseline and every 6 weeks.ResultsA total of 108 participants completed the study, with 55 in the Probucol group. The cohort consisted of 58 (53.7%) women, with a mean age of 58.4 +/- 8.0 (range, 45-80) years. After 12 weeks of treatment, the changes in plasma A beta 42 and sRAGE levels significantly differed between the Probucol and placebo groups (Delta A beta 42: beta = 6.827, P = 0.030; Delta sRAGE: beta = 98.668, P = 0.004). Furthermore, Delta sRAGE was positively correlated with the change in A beta 42 (beta = 0.018, P = 0.048). When adjusted for Delta sRAGE, the effect of Probucol on plasma A beta 42 levels was attenuated (beta = 5.065, P = 0.116). In the Probucol group only, Delta sRAGE was significantly correlated with oxidized low-density lipoproteins (beta = 4.27, P = 0.011), total cholesterol (beta = 67.50, P = 0.046), and low-density lipoproteins (beta = - 91.01, P = 0.011).ConclusionsDaily oral administration of Probucol (1000 mg) for 12 weeks significantly increased plasma A beta 42 levels, likely through modulation of sRAGE. This effect may be attributed to the antioxidant and lipid-lowering properties of Probucol. These findings suggest that Probucol could potentially serve as a protective agent against the pathological processes of AD.Trial registrationThis study was registered on the Chinese Clinical Trial Registry platform in June 2019 (Trial registration number: ChiCTR-1900023542).