对题为“用semaglutide靶向痴呆预防:APOE4纯合子的案例”的信函的回应

IF 13 1区 医学 Q1 CLINICAL NEUROLOGY
Rong Xu
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引用次数: 0

摘要

致编辑:我们很高兴有机会就Daly博士及其同事对我们研究的评论发表意见作者提出了一个有趣的问题,即未来的研究应集中在具有非糖尿病遗传风险谱的高风险患者(载脂蛋白(APOE) ε4纯合子)中检测semaglutide对阿尔茨海默病(AD)的影响。APOE ε4等位基因仍然是散发性AD2最强的遗传危险因素;然而,约45%的痴呆病例与14种可改变的非遗传风险因素有关,包括饮食、缺乏身体活动、糖尿病、肥胖、高血压、高低密度脂蛋白胆固醇、吸烟、饮酒、睡眠障碍和抑郁Semaglutide在治疗多种可改变的AD危险因素方面有益处,包括肥胖、2型糖尿病、心血管和慢性肾脏疾病,并且在治疗吸烟和饮酒方面似乎有希望4-9。新兴研究表明,西马鲁肽具有抗炎和免疫特性10,11,并能改善血管功能。5,12鉴于其针对多种非遗传风险因素和AD近端机制的能力,仅关注APOE ε4纯合子个体可能会忽略其他高危人群的重要机会。然而,我们同意,在具有不同临床和遗传特征(包括APOE基因型)的人群中,西马鲁肽的获益和风险概况可能有所不同;因此,一种精准医疗方法是必要的。作者声明无利益冲突。作者披露可在支持信息中获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Response to the letter titled “Targeting dementia prevention with semaglutide: the case for APOE4 homozygotes”

To the Editor,

We appreciate the opportunity to address Dr. Daly and colleagues’ comments regarding our study.1 The author raised an interesting question that future studies shall focus on testing semaglutide, on Alzheimer's disease (AD) in high-risk patients with a nondiabetic genetic risk profile—those with apolipoprotein (APOE) ε4 homozygotes. The APOE ε4 allele remains the strongest genetic risk factor for sporadic AD2; however, ≈ 45% of dementia cases have been linked to 14 modifiable non-genetic risk factors, including diet, physical inactivity, diabetes, obesity, hypertension, high low-density lipoprotein cholesterol, smoking, alcohol drinking, sleep disorders, and depression.3 Semaglutide has benefits in treating multiple modifiable AD risk factors, including obesity, type 2 diabetes, and cardiovascular and chronic kidney diseases, and appears to be promising for treating smoking and alcohol drinking4-9. Emerging research suggests that semaglutide has anti-inflammatory and immunological properties10, 11 and that it improves vascular function.5, 12 Given its ability to target multiple non-genetic risk factors and proximal mechanisms of AD, focusing exclusively on individuals with APOE ε4 homozygotes may overlook important opportunities in other high-risk populations. However, we agree that the benefit and risk profiles of semaglutide may differ in people with different clinical and genetic characteristics, including APOE genotypes; therefore, a precision medicine approach is warranted.

The author declares no conflicts of interest. Author disclosures are available in the supporting information.

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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
期刊介绍: Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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