Patel Shivani, Thornton Alison, Parmar Mayur S
Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.
Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater, FL, USA.
Mol Neurobiol. 2025 Aug 1. doi: 10.1007/s12035-025-05234-4.
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), and neuroinflammation, leading to progressive cognitive decline. Research has increasingly emphasized the importance of a nutritious diet rich in phytochemicals that promotes brain health and potentially mitigates the risk or progression of neurodegenerative diseases, such as AD. Resveratrol (RSV), a natural polyphenol with known anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective properties, has thus garnered significant attention. This review examines the potential of RSV in modulating AD pathophysiology, drawing from preclinical and clinical investigations. Preclinical studies demonstrate RSV reduces Aβ accumulation by modulating BACE1, enhancing neprilysin activity, inhibiting aggregation, and promoting clearance. RSV also attenuates Tau phosphorylation in animal models, suggesting its potential to target both hallmark AD pathologies. Furthermore, RSV exhibits anti-inflammatory properties by reducing microglial activation and proinflammatory markers. Clinical trials indicate that RSV may attenuate declines in CSF Aβ40 levels and reduce CSF MMP9 levels, indicating potential benefits in Aβ pathology and neuroinflammation in select studies. However, its impact on tau remains inconclusive. Some clinical studies have shown trends toward cognitive benefits, particularly in functional measures such as ADCS-ADL; however, these findings are inconsistent across different cognitive assessments (e.g., MMSE and ADAS-cog). Due to limited and inconsistent clinical evidence, RSV's therapeutic efficacy for AD or mild cognitive impairment (MCI) remains unproven, necessitating larger, well-powered clinical trials in diverse populations to evaluate its potential benefits. RSV holds promise as a potential therapeutic agent. Still, challenges such as poor bioavailability and rapid metabolism require optimized delivery systems and further research to establish clinical efficacy and optimal dosing.
阿尔茨海默病（AD）是一种毁灭性的神经退行性疾病，其特征为β-淀粉样蛋白（Aβ）斑块、神经原纤维缠结（NFTs）和神经炎症，导致进行性认知衰退。研究越来越强调富含促进大脑健康并可能减轻神经退行性疾病（如AD）风险或进展的植物化学物质的营养饮食的重要性。白藜芦醇（RSV）是一种具有抗炎、抗氧化、抗凋亡和神经保护特性的天然多酚，因此受到了广泛关注。本综述借鉴临床前和临床研究，探讨了RSV在调节AD病理生理学方面的潜力。临床前研究表明，RSV通过调节β-分泌酶1（BACE1）、增强中性内肽酶活性、抑制聚集和促进清除来减少Aβ积累。RSV还可减轻动物模型中的Tau磷酸化，表明其有可能针对AD的两种标志性病理。此外，RSV通过减少小胶质细胞活化和促炎标志物表现出抗炎特性。临床试验表明，RSV可能会减轻脑脊液中Aβ40水平的下降，并降低脑脊液中基质金属蛋白酶9（MMP9）的水平，表明在某些研究中对Aβ病理和神经炎症有潜在益处。然而，其对tau的影响尚无定论。一些临床研究显示出认知益处的趋势，特别是在诸如阿尔茨海默病协作研究-日常生活活动量表（ADCS-ADL）等功能测量方面；然而，这些发现在不同的认知评估（如简易精神状态检查表（MMSE）和阿尔茨海默病评定量表-认知部分（ADAS-cog））中并不一致。由于临床证据有限且不一致，RSV对AD或轻度认知障碍（MCI）的治疗效果仍未得到证实，需要在不同人群中进行更大规模、有充分说服力的临床试验来评估其潜在益处。RSV有望成为一种潜在的治疗药物。然而，诸如生物利用度差和代谢迅速等挑战需要优化给药系统，并进行进一步研究以确定临床疗效和最佳剂量。
