Doraiswamy P M, Miller M G, Hellegers C A, Nwosu A, Choe J, Murdoch D M
Neurocognitive Disorders Program, Department of Psychiatry and Behavioural Sciences, Duke University School of Medicine, Durham, NC, USA.
Duke Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, NC, USA.
JAR Life. 2023 Aug 23;12:77-83. doi: 10.14283/jarlife.2023.13. eCollection 2023.
There is a need to develop non-invasive practical lifestyle interventions for preventing Alzheimer's disease (AD) in people at risk, such as those with mild cognitive impairment (MCI). Blueberry consumption has been associated with reduced risk of dementia in some epidemiologic studies and with improvements in cognition in healthy aging adults. Blood-based biomarkers have emerged at the forefront of AD therapeutics research spurred by the development of reliable ultra-sensitive "single-molecule array" assays with 100-1000-fold greater sensitivity over traditional platforms.
The purpose of this study was to examine the effect of blueberry supplementation in MCI on six blood biomarkers: amyloid-beta 40 (Aβ40), amyloid-beta 42 (Aβ42), phosphorylated Tau181 (ptau181), neurofilament light (NfL), Glial Fibrillary acidic protein (GFAP), and Brain-Derived Neurotrophic Factor (BDNF).
This was a 12-week, open-label, pilot trial of 10 participants with MCI (mean age 80.2 years + 5.16). Subjects consumed 36 grams per day of lyophilized blueberry powder in a split dose consumed with breakfast and dinner. Baseline and endpoint venous blood was analyzed using an ultrasensitive SIMOA assay. Our aim was to test if blueberry supplementation would particularly impact p-tau181, NfL, and GFAP elevations associated with the neurodegenerative process.
There were no statistically significant (p < 0.05) changes from baseline to endpoint for any of the biomarker values or in the ratios of Aβ42 / Aβ40 and ptau181/ Aβ42. Adverse effects were mild and transient; supplementation was relatively well tolerated with all subjects completing the study.
To our knowledge, this is the first study to prospectively examine the effects of blueberry supplementation on a panel of blood biomarkers reflecting the neurodegenerative process. Our findings raise two possibilities - a potential stabilization of the neurodegenerative process or a lack of a direct and acute effect on beta-amyloid/tau/glial markers. A larger controlled study is warranted.
有必要开发非侵入性的实用生活方式干预措施，以预防有患病风险人群（如轻度认知障碍[MCI]患者）患阿尔茨海默病（AD）。在一些流行病学研究中，食用蓝莓与降低痴呆风险有关，并且与健康老年人的认知改善有关。随着可靠的超灵敏“单分子阵列”检测方法的发展，其灵敏度比传统平台高100至1000倍，基于血液的生物标志物已成为AD治疗研究的前沿领域。
本研究的目的是检验蓝莓补充剂对MCI患者的六种血液生物标志物的影响：β淀粉样蛋白40（Aβ40）、β淀粉样蛋白42（Aβ42）、磷酸化Tau181（ptau181）、神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）。
这是一项为期12周的开放标签试点试验，有10名MCI患者（平均年龄80.2岁±5.16岁）参与。受试者每天分两次服用36克冻干蓝莓粉，分别在早餐和晚餐时服用。使用超灵敏的单分子阵列（SIMOA）检测方法分析基线和终点时的静脉血。我们的目的是测试蓝莓补充剂是否会特别影响与神经退行性过程相关的p-tau181、NfL和GFAP升高。
任何生物标志物的值从基线到终点均无统计学显著变化（p<0.05），Aβ42/Aβ40和ptau181/Aβ42的比值也无变化。不良反应轻微且短暂；所有受试者均完成研究，补充剂耐受性相对良好。
据我们所知，这是第一项前瞻性研究蓝莓补充剂对一组反映神经退行性过程的血液生物标志物影响的研究。我们的研究结果提出了两种可能性——神经退行性过程可能得到稳定，或者对β淀粉样蛋白/ Tau/胶质细胞标志物缺乏直接和急性影响。有必要进行更大规模的对照研究。
