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在一个由不同种族组成的老年人群体中,肌肉生长抑制素与血浆β-淀粉样蛋白 42/40 水平之间的关联。

Associations Between Circulating Levels of Myostatin and Plasma β-Amyloid 42/40 in a Biracial Cohort of Older Adults.

机构信息

Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

出版信息

J Gerontol A Biol Sci Med Sci. 2023 Oct 28;78(11):2077-2082. doi: 10.1093/gerona/glad132.

Abstract

BACKGROUND

Myostatin, a cytokine produced by skeletal muscle, may influence Alzheimer's disease (AD) pathogenesis, but sparse evidence exists in humans. We assessed the association between circulating levels of myostatin at Year 1 and plasma levels of β-amyloid 42/40 at Year 2, a marker of AD pathology, in a biracial cohort of older adults.

METHODS

We studied 403 community-dwelling older adults enrolled in the Health, Aging and Body Composition Study from Memphis, Tennessee, and Pittsburgh, PA. Mean age was 73.8 ± 3 years; 54% were female; and 52% were Black. Serum myostatin levels were measured at Year 1, plasma β-amyloid 42/40 levels in Year 2 (higher ratio indicating lower amyloid load). Multivariable linear regression analyses tested the association of serum myostatin with plasma levels of β-amyloid 42/40 adjusted for computed-tomography-derived thigh muscle cross-sectional area, demographics, APOe4 allele, and risk factors for dementia. We tested for 2-way.interactions between myostatin and race or sex; results were stratified by race and sex.

RESULTS

In multivariable models, myostatin was positively associated with plasma levels of β-amyloid 42/40 (standardized regression coefficient: 0.145, p = .004). Results were significant for white men and women (0.279, p = .009, and 0.221, p = .035, respectively) but not for Black men or women; interactions by race and gender were not statistically significant.

CONCLUSIONS

Higher serum myostatin was associated with lower amyloid burden, independently of APOe4 alleles, muscle area and other established risk factors for dementia. The role of myostatin in AD pathogenesis and the influence of race should be further investigated.

摘要

背景

肌肉生长抑制素(Myostatin)是一种由骨骼肌产生的细胞因子,可能会影响阿尔茨海默病(AD)的发病机制,但人类的相关证据很少。我们评估了 1 年内循环肌生成抑制素水平与 2 年内 AD 病理标志物β-淀粉样蛋白 42/40 血浆水平之间的关联,研究对象为孟菲斯田纳西州和匹兹堡宾夕法尼亚州的健康老龄化和身体成分研究中的一个双种族队列的老年人。

方法

我们研究了 403 名居住在田纳西州孟菲斯市和宾夕法尼亚州匹兹堡市的社区居住的老年人,他们参加了健康、老龄化和身体成分研究。平均年龄为 73.8 ± 3 岁;54%为女性;52%为黑人。在第 1 年测量血清肌生成抑制素水平,在第 2 年测量血浆β-淀粉样蛋白 42/40 水平(比值越高表示淀粉样蛋白负荷越低)。多变量线性回归分析测试了血清肌生成抑制素与血浆β-淀粉样蛋白 42/40 水平之间的关联,调整了计算机断层扫描(CT)衍生的大腿肌肉横截面积、人口统计学、APOE4 等位基因以及痴呆风险因素。我们测试了肌生成抑制素与种族或性别之间的双向相互作用;结果按种族和性别进行分层。

结果

在多变量模型中,肌生成抑制素与血浆β-淀粉样蛋白 42/40 水平呈正相关(标准化回归系数:0.145,p =.004)。这一结果在白人男性和女性中显著(0.279,p =.009 和 0.221,p =.035),但在黑人男性和女性中不显著;种族和性别之间的相互作用没有统计学意义。

结论

较高的血清肌生成抑制素与较低的淀粉样蛋白负荷独立相关,与 APOE4 等位基因、肌肉面积和其他已知的痴呆风险因素无关。肌生成抑制素在 AD 发病机制中的作用以及种族的影响应进一步研究。

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