Neuroprotective Effect of Trans-Resveratrol in Mild to Moderate Alzheimer Disease: A Randomized, Double-Blind Trial

Jiachen Gu; Zongshan Li; Huimin Chen; Xiaomin Xu; Yongang Li; Yaxing Gui

doi:10.1007/s40120-021-00271-2

Neuroprotective Effect of Trans-Resveratrol in Mild to Moderate Alzheimer Disease: A Randomized, Double-Blind Trial

Neurol Ther. 2021 Dec;10(2):905-917. doi: 10.1007/s40120-021-00271-2. Epub 2021 Aug 16.

Authors

Jiachen Gu¹, Zongshan Li², Huimin Chen², Xiaomin Xu², Yongang Li^{2

3}, Yaxing Gui⁴

Affiliations

¹ Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
³ Department of Neurology, First People' Hospital of Wenling, Wenling, China.
⁴ Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. YaxingGui@shsmu.edu.cn.

Abstract

Introduction: Amyloid-beta (Aβ) protein is a major component of the extracellular plaque found in the brains of individuals with Alzheimer's disease (AD). In this study, we investigated the effect of trans-resveratrol as an antagonist treatment for moderate to mild AD, as well as its safety and tolerability.

Methods: This was a case-control study that enrolled 30 selected patients who had been clinically diagnosed with moderate to mild AD. These patients were randomly divided into two groups, namely, a placebo group (n = 15) and a trans-resveratrol group (n = 15) who received 500 mg trans-resveratrol orally once daily for 52 weeks. Brain magnetic resonance imaging (MRI) examinations were performed on and cerebrospinal fluid (CSF) samples were obtained from all participants before (baseline) and after the study (52 weeks). Enzyme-linked immunosorbent assays were used to determine the levels of plasma Aβ40 and Aβ42 and CSF Aβ40 and Aβ42.

Results: The results showed that the changes over the study period in the levels of Aβ40 in the blood and CSF of the patients treated with trans-resveratrol were not statistically significant (P > 0.05). In contrast, patients who received placebo showed a significant decrease in Aβ40 levels compared with that at the beginning of the study (CSF Aβ40: P = 0.024, plasma Aβ40: P = 0.036). Analysis of the images on the brain MRI scans revealed that the brain volume of the patients treated with trans-resveratrol was significantly reduced at 52 weeks (P = 0.011) compared with that of patients in the placebo treatment group, Further analysis indicated that the level of matrix metallopeptidase 9 in the CSF of the patients treated with trans-resveratrol at 52 weeks decreased by 46% compared with that of patients in the placebo group (P = 0.033).

Conclusion: These results indicate that trans-resveratrol has potential neuroprotective roles in the treatment of moderate to mild AD and that its mechanism may involve a reduction in the accumulation and toxicity of Aβ in the brain of patients, thereby reducing neuroinflammation.

Trial registration: Chinese clinical trial registry: CTR20151780X.

Keywords: Alzheimer disease; Amyloid Beta; MMP-9; Trans-resveratrol.