Zhu Yao, Wu Yan, Lv Xinyi, Wu Jiaonan, Shen Chunzi, Tang Qiqiang, Wang Guoping
Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
CNS Neurosci Ther. 2024 Jan;30(1):e14401. doi: 10.1111/cns.14401. Epub 2023 Aug 14.
To investigate whether insula network connectivity modulates the relationship between apolipoprotein E (APOE) ε4 genotype, cerebrospinal fluid (CSF) biomarkers (Aβ, Tau, and pTau) and cognition across Alzheimer's disease (AD) spectrum.
Forty-six cognitive normal (CN), 35 subjective memory complaint (SMC), 41 mild cognitive impairment (MCI), and 32 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were obtained. Multivariable linear regression analyses were conducted to investigate the main effects and interaction of the APOE genotype and disease status on the insula functional connectivity (IFC) network. Mediation and moderation analysis were performed to investigate whether IFC strengths regulate the association between APOE genotype, CSF biomarkers and cognition. Additionally, the support vector machine (SVM) model integrating APOE genotype, CSF biomarkers, and neuroimaging biomarkers (insula volumes and altered regional IFCs) was used to classify the AD spectrum.
The interactive effect of the APOE genotype and disease on the insula network was found in the left medial superior frontal gyrus (SFGmed.L), right anterior medial prefrontal cortex (aMPFC.R), and bilateral thalamus (THA.B). The functional connectivities (FCs) in the left insula (LIns) connecting with the left posterior middle temporal gyrus (pMTG.L), SFGmed.L, and right lingual gyrus (LING.R) were correlated with cognition. LIns-SFGmed.L and LIns-pMTG.L FCs could moderate the effects of Tau on cognition. Furthermore, LIns-SFGmed.L FC may suppress the association between APOE genotype and cognition. More importantly, the integrated biomarkers from the SVM model yielded strong powers for classifying the AD spectrum.
Insula functional connectivity regulated the association between APOE genotype, CSF Tau and cognition and provided stage-dependent biomarkers for early differentiation of the AD spectrum. The present study used a cross-sectional design. Follow-up studies are needed to validate the relationship.
研究脑岛网络连通性是否调节载脂蛋白E（APOE）ε4基因型、脑脊液（CSF）生物标志物（Aβ、Tau和pTau）与阿尔茨海默病（AD）谱系中认知之间的关系。
从阿尔茨海默病神经影像倡议（ADNI）中获取了46名认知正常（CN）者、35名主观记忆障碍（SMC）者、41名轻度认知障碍（MCI）者和32名AD患者。进行多变量线性回归分析，以研究APOE基因型和疾病状态对脑岛功能连通性（IFC）网络的主要影响和相互作用。进行中介和调节分析，以研究IFC强度是否调节APOE基因型、CSF生物标志物与认知之间的关联。此外，使用整合了APOE基因型、CSF生物标志物和神经影像生物标志物（脑岛体积和改变的区域IFC）的支持向量机（SVM）模型对AD谱系进行分类。
在左侧额上回内侧（SFGmed.L）、右侧前额叶内侧前部皮质（aMPFC.R）和双侧丘脑（THA.B）发现了APOE基因型和疾病对脑岛网络的交互作用。左侧脑岛（LIns）与左侧颞中回后部（pMTG.L）、SFGmed.L和右侧舌回（LING.R）之间的功能连通性（FCs）与认知相关。LIns-SFGmed.L和LIns-pMTG.L的FCs可以调节Tau对认知的影响。此外，LIns-SFGmed.L的FC可能抑制APOE基因型与认知之间的关联。更重要的是，SVM模型的整合生物标志物在对AD谱系进行分类方面具有很强的能力。
脑岛功能连通性调节了APOE基因型、CSF Tau与认知之间的关联，并为AD谱系的早期区分提供了阶段依赖性生物标志物。本研究采用横断面设计。需要进行后续研究来验证这种关系。
