白细胞表面生物标志物提示散发性阿尔茨海默病固有免疫缺陷。
Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease.
机构信息
The Florey Institute of Neuroscience, the University of Melbourne, Parkville, Victoria, Australia.
The Australian e-Health Research Centre, CSIRO, Brisbane, Queensland, Australia.
出版信息
Alzheimers Dement. 2023 May;19(5):2084-2094. doi: 10.1002/alz.12813. Epub 2022 Nov 9.
INTRODUCTION
Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk individuals for therapeutic interventions.
METHODS
In three stages, a total of 34 leukocyte antigens were examined by flow cytometry immunophenotyping. Data were analyzed by logistic regression and receiver operating characteristic (ROC) analyses.
RESULTS
We identified leukocyte markers differentially expressed in the patients with AD. Pathway analysis revealed a complex network involving upregulation of complement inhibition and downregulation of cargo receptor activity and Aβ clearance. A proposed panel including four leukocyte markers - CD11c, CD59, CD91, and CD163 - predicts patients' PET Aβ status with an area under the curve (AUC) of 0.93 (0.88 to 0.97). CD163 was the top performer in preclinical models. These findings have been validated in two independent cohorts.
CONCLUSION
Our finding of changes on peripheral leukocyte surface antigens in AD implicates the deficit in innate immunity. Leukocyte-based biomarkers prove to be both sensitive and practical for AD screening and diagnosis.
简介
在散发性阿尔茨海默病（AD）中，基于血液的诊断和预后对于识别有治疗干预风险的个体非常重要。
方法
通过流式细胞术免疫表型分析，共检查了 34 种白细胞抗原。通过逻辑回归和接收者操作特征（ROC）分析对数据进行了分析。
结果
我们确定了 AD 患者中差异表达的白细胞标记物。通路分析显示，涉及补体抑制上调和货物受体活性以及 Aβ清除下调的复杂网络。一个包括四个白细胞标记物（CD11c、CD59、CD91 和 CD163）的拟议面板，预测了患者的 PET Aβ状态，曲线下面积（AUC）为 0.93（0.88 至 0.97）。CD163 在临床前模型中表现最佳。这些发现已经在两个独立的队列中得到了验证。
结论
我们在 AD 外周白细胞表面抗原上发现的变化表明先天免疫缺陷。基于白细胞的生物标志物被证明对 AD 的筛查和诊断具有敏感性和实用性。
Zotero 插件