干血斑中阿尔茨海默病和神经退行性变的生物标志物-远程设置的新采集方法。

Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings.

机构信息

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Shagreens Academy at the University of Gothenburg, Mölndal, Sweden.

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

出版信息

Alzheimers Dement. 2024 Apr;20(4):2340-2352. doi: 10.1002/alz.13697. Epub 2024 Jan 29.

DOI:10.1002/alz.13697

PMID:38284555

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11032540/

Abstract

BACKGROUND

We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPS ) for the diagnosis and monitoring of neurodegenerative diseases in remote settings.

METHODS

In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p-tau181 and p-tau217) were measured in paired DPS and ethylenediaminetetraacetic acid plasma samples with single-molecule array. In the validation cohort, a subset of participants (n = 99) had cerebrospinal fluid (CSF) biomarkers.

RESULTS

All DPS and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPS GFAP, NfL, p-tau181, and p-tau217 differed between CSF Aβ-positive and -negative individuals and were associated with worsening cognition.

DISCUSSION

Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPS extends the utility of blood-based biomarkers to remote settings with simplified sampling conditions, storage, and logistics.

HIGHLIGHTS

A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPS). DPS biomarkers correlated with standard procedures and cognitive status. DPS biomarkers had a good diagnostic accuracy discriminating amyloid status. Our findings show the potential interchangeability of DPS and plasma sampling. DPS may facilitate remote and temperature-independent sampling for AD biomarker measurement. Innovative tools for blood biomarker sampling may help recognizing the earliest changes of AD.

摘要

背景

我们旨在评估从静脉干血斑（DPS）中测量阿尔茨海默病（AD）和神经退行性变生物标志物的精确性，以便在偏远地区对神经退行性疾病进行诊断和监测。

方法

在发现队列（n=154）和验证队列（n=115）中，使用单分子阵列测量了配对的 DPS 和乙二胺四乙酸血浆样本中的神经胶质纤维酸性蛋白（GFAP）；神经丝轻链（NfL）；β淀粉样蛋白（Aβ）40、Aβ42；和磷酸化 tau（p-tau181 和 p-tau217）。在验证队列中，一部分参与者（n=99）进行了脑脊液（CSF）生物标志物检测。

结果

除了 Aβ42 之外，所有 DPS 和血浆分析物均显著相关。在验证队列中，DPS GFAP、NfL、p-tau181 和 p-tau217 在 CSF Aβ阳性和阴性个体之间存在差异，与认知能力下降有关。

讨论

我们的数据表明，从 DPS 测量与 AD 病理和神经退行性变相关的血液生物标志物，扩展了基于血液的生物标志物在简化采样条件、存储和物流的偏远地区的应用。

重点

在干血斑（DPS）中可检测到与阿尔茨海默病（AD）和神经退行性变相关的多种生物标志物。DPS 生物标志物与标准程序和认知状态相关。DPS 生物标志物具有良好的诊断准确性，可区分淀粉样状态。我们的发现表明 DPS 和血浆采样之间具有潜在的可互换性。DPS 可能有助于 AD 生物标志物测量的远程和温度独立采样。血液生物标志物采样的创新工具可能有助于识别 AD 的最早变化。