Extracellular vesicle biomarkers of Alzheimer's disease associated with sub-clinical cognitive decline in late middle age.

Extracellular vesicle biomarkers of Alzheimer's disease associated with sub-clinical cognitive decline in late middle age.
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阿尔茨海默氏病的细胞外囊泡生物标志物与中期晚期临界认知下降有关。

DOI:
10.1002/alz.12130
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发表时间:
2020-09
期刊:
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子:
--
通讯作者:
Kapogiannis D
Kapogiannis D
中科院分区:
其他
文献类型:
--
作者:
Eren E;Hunt JFV;Shardell M;Chawla S;Tran J;Gu J;Vogt NM;Johnson SC;Bendlin BB;Kapogiannis D

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神经元细胞外囊泡(nEV)tau和胰岛素信号传导生物标志物可以检测临床前阿尔茨海默病和年龄相关的认知衰退。这项病例对照研究使用了来自威斯康星州阿尔茨海默病预防登记处的73名认知下降和73名稳定参与者(62.4 ± 6.3岁)的重复血清样本。我们免疫捕获nEV;测量tau和胰岛素信号传导生物标志物;并按组检查生物标志物差异,它们在训练和测试数据集中的组分类中的表现(分别为97、49个个体),以及它们是否预测认知表现变化。与稳定个体相比,下降显示基线总、p231-和p181-tau随年龄增长而升高,p-IR和p-IGF-1 R的年变化也较高。在训练数据中,组合生物标志物以94%的曲线下面积(AUC)、86.0%的灵敏度和86.7%的特异性分类下降者,在测试数据中,组合生物标志物以75%的AUC、71.4%的灵敏度和77.3%的特异性分类下降者。胰岛素生物标志物可预测认知能力的变化。结合nEV生物标志物可以识别与年龄相关的认知衰退的个体。
Neuronal extracellular vesicle (nEV) tau and insulin signaling biomarkers may detect preclinical Alzheimer's disease and age‐associated cognitive decline. This case‐control study used repeated serum samples from 73 cognitively declining and 73 stable Wisconsin Registry for Alzheimer's Prevention participants (62.4 ± 6.3 years old). We immunocaptured nEVs; measured tau and insulin signaling biomarkers; and examined biomarker differences by group, their performance in group classification in training and test datasets (97, 49 individuals, respectively), and whether they predict cognitive performance change. Declining compared to stable individuals showed higher baseline total, p231‐, and p181‐tau with older age and higher annualized change for p‐IR and p‐IGF‐1R. Combining biomarkers classified decliners with 94% area under the curve (AUC), 86.0% sensitivity and 86.7% specificity, in training data, and 75% AUC, 71.4% sensitivity, and 77.3% specificity, in test data. Insulin biomarkers predicted cognitive performance change prospectively. Combining nEV biomarkers can identify individuals with age‐associated cognitive decline.
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