Lin Chieh-Hsin, Lane Hsien-Yuan
Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No.123, Dapi Road, Niaosong District, Kaohsiung City, 833401, Taiwan.
School of Medicine, Chang Gung University, No.259, Wenhua 1st Road, Guishan Dist., Taoyuan City, 33302, Taiwan.
Transl Psychiatry. 2025 Aug 5;15(1):264. doi: 10.1038/s41398-025-03492-3.
With the recent approval of anti-amyloid beta (Aβ) monoclonal antibody infusion therapies for Alzheimer's disease (AD), more feasible and safter Aβ-reducing approaches are anticipated. Previous studies showed that 750-mg/day or 1000-mg/day (but not 500-mg/day) sodium benzoate treatment improved cognitive function in AD patients with excellent safety and that benzoate decreased Aβ burden in an animal AD model. The current study aimed to explore whether oral sodium benzoate was able to reduce Aβ peptides in AD patients and whether Aβ before treatment was correlated with cognitive improvement after treatment. This secondary analysis used data from a double-blind trial, in which 149 patients with mild AD were randomized to receive oral placebo or one of three benzoate doses (500, 750, or 1000 mg/day). Cognitive function and plasma Aβ 1-40 and Aβ 1-42 levels were measured before and after treatment. When compared to placebo, benzoate therapy at effective doses (750 and 1000 mg/day) reduced Aβ 1-40 and the sum of both Aβ peptides (Aβ 1-40 plus Aβ 1-42) in AD patients. Moreover, higher Aβ 1-42 levels at baseline were associated with better cognitive improvements after benzoate treatment at effective doses in the patients. The findings suggest that sodium benzoate therapy can reduce Aβ 1-40 and the total Aβ in AD patients and higher Aβ 1-42 levels before treatment predict better cognitive improvements. Due to its superior safety and convenient administration, sodium benzoate has the potential to be a novel Aβ-reducing therapy for AD treatment. TRIAL REGISTRATION: Name of trial registry: NMDA Enhancer for the Treatment of Mild Alzheimer's Disease. Identifying number: ClinicalTrials.gov Identifier: NCT03752463 ( https://clinicaltrials.gov/ct2/show/NCT03752463 ). Registration date: 2018-11-21.
随着抗淀粉样蛋白β（Aβ）单克隆抗体输注疗法最近被批准用于治疗阿尔茨海默病（AD），人们期待更可行、更安全的降低Aβ的方法。先前的研究表明，每天750毫克或1000毫克（而非500毫克）苯甲酸钠治疗可改善AD患者的认知功能，且安全性良好，并且苯甲酸盐可降低动物AD模型中的Aβ负担。当前研究旨在探讨口服苯甲酸钠是否能够降低AD患者的Aβ肽，以及治疗前的Aβ水平是否与治疗后的认知改善相关。这项二次分析使用了一项双盲试验的数据，在该试验中，149例轻度AD患者被随机分配接受口服安慰剂或三种苯甲酸钠剂量（500、750或1000毫克/天）之一。在治疗前后测量认知功能以及血浆Aβ 1-40和Aβ 1-42水平。与安慰剂相比，有效剂量（750和1000毫克/天）的苯甲酸盐治疗可降低AD患者的Aβ 1-40以及两种Aβ肽（Aβ 1-40加Aβ 1-42）的总和。此外，在患者中，基线时较高的Aβ 1-42水平与有效剂量苯甲酸盐治疗后更好的认知改善相关。这些发现表明，苯甲酸钠治疗可降低AD患者的Aβ 1-40和总Aβ水平，并且治疗前较高水平的Aβ 1-42可预测更好的认知改善。由于其卓越的安全性和便捷的给药方式，苯甲酸钠有潜力成为一种新型的用于AD治疗的降低Aβ的疗法。试验注册：试验注册名称：用于治疗轻度阿尔茨海默病的NMDA增强剂。识别号：ClinicalTrials.gov标识符：NCT03752463（https://clinicaltrials.gov/ct2/show/NCT03752463）。注册日期：2018年11月21日。
