Dysfunction in the hierarchy of morphometric similarity network in Alzheimer's disease and its correlation with cognitive performance and gene expression profiles.

IF 5.9 2区 医学 Q1 PSYCHIATRY
Chuchu Zheng, Wei Zhao, Zeyu Yang, Shuixia Guo
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引用次数: 0

Abstract

Background: Previous research has shown abnormal functional network gradients in Alzheimer's disease (AD). Structural network gradient is capable of capturing continuous changes in brain morphology and has the ability to elucidate the underlying processes of neurodevelopment. However, it remains unclear whether structural network gradients are altered in AD and what associations exist between these changes and cognitive function, and gene expression profiles.

Methods: By constructing an individualized structural network gradient decomposition framework, we calculated the morphological similarity network (MSN) gradients for 404 subjects (186 AD patients and 218 normal controls). We investigated AD-related alterations in MSN gradients, along with the associations between MSN gradients and cognitive function, MSN topological properties, and gene expression profiles.

Results: Our findings indicated that the principal MSN gradient alterations in AD were primarily characterized by an increase in the primary and secondary sensory cortices and a decrease in the association cortex 1. The primary and higher-order cortices exhibited opposite associations with cognition, including executive function, language skills, and memory processes. Moreover, the principal MSN gradients were found to significantly predict cognitive function in AD. The altered gradient pattern was 14.8% attributable to gene expression profiles, and the genes demonstrating the highest correlation are involved in metabolic activity and synaptic signaling.

Conclusions: Our results offered novel insights into the underlying mechanisms of structural brain network impairment in AD patients, enhancing our understanding of the neurobiological processes responsible for impaired cognition in patients with AD, and offering a new dimensional structural biomarker for AD.

阿尔茨海默病形态相似性网络层级功能障碍及其与认知能力和基因表达谱的相关性
背景:以往的研究显示阿尔茨海默病(AD)的功能网络梯度异常。结构网络梯度能够捕捉大脑形态的连续变化,并有能力阐明神经发育的潜在过程。然而,尚不清楚AD是否改变了结构网络梯度,以及这些变化与认知功能和基因表达谱之间存在什么关联。方法:通过构建个性化结构网络梯度分解框架,计算404例AD患者(186例)和正常人(218例)的形态相似网络(MSN)梯度。我们研究了ad相关的MSN梯度变化,以及MSN梯度与认知功能、MSN拓扑特性和基因表达谱之间的关系。结果:我们的研究结果表明,阿尔茨海默病的主要MSN梯度改变主要表现为初级和次级感觉皮层的增加以及关联皮层的减少。初级和高阶皮层在认知方面表现出相反的关联,包括执行功能、语言技能和记忆过程。此外,主MSN梯度被发现可以显著预测AD患者的认知功能。14.8%的梯度模式改变可归因于基因表达谱,其中相关性最高的基因涉及代谢活性和突触信号传导。结论:我们的研究结果为阿尔茨海默病患者脑结构网络损伤的潜在机制提供了新的见解,增强了我们对阿尔茨海默病患者认知功能受损的神经生物学过程的理解,并为阿尔茨海默病患者提供了新的维度结构生物标志物。
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来源期刊
Psychological Medicine
Psychological Medicine 医学-精神病学
CiteScore
11.30
自引率
4.30%
发文量
711
审稿时长
3-6 weeks
期刊介绍: Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.
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