Relationship between Plasma Analytes and SPARE-AD Defined Brain Atrophy Patterns in ADNI

Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD). However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP®) and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD) at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

多种炎症与代谢通路均与阿尔茨海默病（Alzheimer's Disease, AD）存在关联。然而直至近年，用于在经过充分表型表征的队列中检测大量分子的多分析物检测面板才得以问世。此类检测面板有助于筛选出指向受累通路的相关分子。本研究针对阿尔茨海默病神经影像倡议（Alzheimer's Disease Neuroimaging Initiative, ADNI）队列的受试者，分析了血浆生物标志物检测面板（Human DiscoveryMAP®）与基线时通过已发表指数SPARE-AD定义的AD样脑萎缩模式之间的关联。共有818名受试者获得了MRI衍生的SPARE-AD评分，其中69%的受试者完成了血浆生物标志物检测，51%的受试者完成了脑脊液（Cerebrospinal Fluid, CSF）tau蛋白与β淀粉样蛋白（Amyloid-beta, Aβ）的检测。在校正后的模型中，我们分析了具有统计学意义的分析物与SPARE-AD评分之间以及各分析物间的相关性。血浆皮质醇与嗜铬粒蛋白A呈现出显著关联，但在校正脑脊液特征的模型中，该关联不再具有统计学意义。血浆巨噬细胞抑制蛋白-1α与胰岛素样生长因子结合蛋白2在校正模型中与脑萎缩呈现显著关联。皮质醇水平与处理速度相关检测呈负相关。本研究结果显示，应激与胰岛素应答，以及与轻度认知障碍-阿尔茨海默病（Mild Cognitive Impairment, MCI-AD）中炎症细胞招募相关的细胞因子，均与特征性AD样脑萎缩模式相关，且与临床症状变化或脑脊液生物标志物存在关联。