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认知障碍和痴呆症背景下血管生成的新标志物。

Novel Markers of Angiogenesis in the Setting of Cognitive Impairment and Dementia.

机构信息

Indiana University Center for Aging Research, Indianapolis, IN, USA.

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

出版信息

J Alzheimers Dis. 2020;75(3):959-969. doi: 10.3233/JAD-191293.

Abstract

BACKGROUND

Aberrant angiogenesis may play a role in the development of Alzheimer's disease and related dementia.

OBJECTIVE

To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults.

METHODS

Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer's disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-β peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity.

RESULTS

Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities.

CONCLUSION

We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.

摘要

背景

异常的血管生成可能在阿尔茨海默病和相关痴呆的发展中起作用。

目的

探讨老年人血管生成活性与神经退行性变证据之间的关系。

方法

对 49 名临床表现为认知正常、轻度认知障碍或早期阿尔茨海默病的老年人进行横断面研究。除神经影像学外,我们还完成了外周血检测,包括血管内皮生长因子、肿瘤坏死因子、成纤维细胞生长因子和淀粉样蛋白-β肽 40。我们使用先进的多色流式细胞术对循环单核细胞进行表型分析,以评估血管生成活性。

结果

尽管我们记录了认知表现、神经影像学结构变化以及正电子发射断层扫描显示的淀粉样蛋白和 tau 负担的差异,但各组之间的血管生成活性没有差异。有趣的是,轻度认知障碍患者的 VEGF 水平升高。在控制年龄、性别、颅内体积和单核细胞亚群的协方差分析模型中,血管生成活性与脑白质高信号增加相关。

结论

我们证明了血管生成活性与脑血管疾病之间存在显著关联。为了更好地理解血管生成作为干预靶点的潜力,需要进行纵向研究。

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