阿尔茨海默病中磷脂酰乙醇胺结合蛋白 1（PEBP1）：ELISA 开发与临床验证。

Phosphatidylethanolamine Binding Protein 1 (PEBP1) in Alzheimer's Disease: ELISA Development and Clinical Validation.

机构信息

Laboratory of Clinical Neurochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

Section of Physiology and Biochemistry, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

出版信息

J Alzheimers Dis. 2022;88(4):1459-1468. doi: 10.3233/JAD-220323.

DOI:10.3233/JAD-220323

PMID:35786656

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9484123/

Abstract

BACKGROUND

Phosphatidylethanolamine binding protein 1 (PEBP1) is a multifunctional protein, mainly known for its specific binding of phosphatidylethanolamine and the ability to suppress the Raf1-MAPK pathway. Its potential role as an Alzheimer's disease (AD) biomarker has been proposed in several studies. However, evaluation of its discriminative value in clinical cohorts is missing.

OBJECTIVE

We aimed to develop a new immunoassay for the measurement of PEBP1 in cerebrospinal fluid (CSF) and assess the possible role of this protein as AD biomarker.

METHODS

We developed a sandwich enzyme-linked immunosorbent assay (ELISA) for detection of PEBP1 in CSF and performed a technical and a clinical validation on two well-characterized cohorts. The first cohort included 14 mild cognitive impairment due to AD (MCI-AD) and 11 other neurological diseases (OND) patients. The second, larger cohort, included 25 MCI-AD, 29 AD dementia (AD-dem), and 21 OND patients.

RESULTS

PEBP1 is highly sensitive to pre-analytical conditions, especially to prolonged storage at room temperature or 4°C. Analysis of the first cohort showed a trend of an increase of PEBP1 level in MCI-AD patients versus OND subjects. Analysis of the second cohort did not show significant differences among diagnostic groups. Weak, positive correlation was found between CSF PEBP1 and t-tau, p-tau, and Aβ40 in the AD-dem group.

CONCLUSION

A novel ELISA for the detection of PEBP1 in CSF was developed. Further research is needed to assess the potential of PEBP1 in AD diagnostics. The observed dependence of the PEBP1 signal on operating procedures encourages its potential application as CSF quality control.

摘要

背景

磷酸乙醇胺结合蛋白 1（PEBP1）是一种多功能蛋白，主要因其对磷酸乙醇胺的特异性结合以及抑制 Raf1-MAPK 通路的能力而闻名。已有多项研究提出其作为阿尔茨海默病（AD）生物标志物的潜在作用。然而，评估其在临床队列中的区分价值尚缺乏研究。

目的

我们旨在开发一种新的脑脊液（CSF）中 PEBP1 测量免疫测定法，并评估该蛋白作为 AD 生物标志物的可能作用。

方法

我们开发了一种用于 CSF 中 PEBP1 检测的夹心酶联免疫吸附测定法（ELISA），并在两个特征明确的队列中进行了技术和临床验证。第一个队列包括 14 名 AD 所致轻度认知障碍（MCI-AD）和 11 名其他神经疾病（OND）患者。第二个更大的队列包括 25 名 MCI-AD、29 名 AD 痴呆（AD-dem）和 21 名 OND 患者。

结果

PEBP1 对分析前条件高度敏感，尤其是在室温或 4°C 下长时间储存时。对第一个队列的分析显示，MCI-AD 患者的 PEBP1 水平呈上升趋势，与 OND 组相比存在趋势性差异。对第二个队列的分析未显示诊断组之间的显著差异。在 AD-dem 组中发现 CSF PEBP1 与 t-tau、p-tau 和 Aβ40 之间存在微弱的正相关。