阿尔茨海默病患者血浆肝型脂肪酸结合蛋白与淀粉样β和tau 水平的相关性。

The Correlations of Plasma Liver-Type Fatty Acid-Binding Protein with Amyloid-β and Tau Levels in Patients with Alzheimer's Disease.

机构信息

Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China.

Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China.

出版信息

J Alzheimers Dis. 2022;88(1):375-383. doi: 10.3233/JAD-220126.

DOI:10.3233/JAD-220126

PMID:35599489

Abstract

BACKGROUND

The dysregulation of lipid metabolism plays an important role in the pathogenesis of Alzheimer's disease (AD). Liver-type fatty acid-binding protein (L-FABP, also known as FABP1) is critical for fatty acid transport and may be involved in AD.

OBJECTIVE

To investigate whether the FABP1 level is altered in patients with AD, and its associations with levels of amyloid-β (Aβ) and tau in the plasma and cerebrospinal fluid (CSF).

METHODS

A cross-sectional study was conducted in a Chinese cohort consisting of 39 cognitively normal controls and 47 patients with AD. The levels of FABP1 in plasma, and Aβ and tau in CSF, were measured by enzyme-linked immunosorbent assay (ELISA). A single-molecule array (SIMOA) was used to detect plasma Aβ levels.

RESULTS

The level of plasma FABP1 was significantly elevated in the AD group (p = 0.0109). Further analysis showed a positive correlation of FABP1 with CSF total tau (t-tau) and phosphorylated tau (p-tau) levels. Besides, plasma FABP1/Aβ42 (AUC = 0.6794, p = 0.0071) and FABP1/t-tau (AUC = 0.7168, p = 0.0011) showed fair diagnostic efficacy for AD. When combined with other common AD biomarkers including plasma Aβ42, Aβ40, and t-tau, both FABP1/Aβ42 and FABP1/t-tau showed better diagnostic efficacy than using these biomarkers alone. Among all AUC analyses, the combination of plasma FABP1/t-tau and Aβ42 had the highest diagnostic value (AUC = 0.8075, p < 0.0001).

CONCLUSION

These findings indicate that FABP1 may play a role in AD pathogenesis and be worthy of further investigation in the future.

摘要

背景

脂代谢失调在阿尔茨海默病（AD）的发病机制中起着重要作用。肝型脂肪酸结合蛋白（L-FABP，也称为 FABP1）对脂肪酸的运输至关重要，并且可能与 AD 有关。

目的

研究 FABP1 水平是否在 AD 患者中发生改变，及其与血浆和脑脊液（CSF）中淀粉样蛋白-β（Aβ）和 tau 的水平的关系。

方法

在中国队列中进行了一项横断面研究，该队列包括 39 名认知正常对照者和 47 名 AD 患者。通过酶联免疫吸附试验（ELISA）测量血浆中 FABP1 以及 CSF 中 Aβ和 tau 的水平。使用单分子阵列（SIMOA）检测血浆 Aβ 水平。

结果

AD 组的血浆 FABP1 水平显著升高（p=0.0109）。进一步分析显示，FABP1 与 CSF 总 tau（t-tau）和磷酸化 tau（p-tau）水平呈正相关。此外，血浆 FABP1/Aβ42（AUC=0.6794，p=0.0071）和 FABP1/t-tau（AUC=0.7168，p=0.0011）对 AD 具有良好的诊断效能。当与其他常见的 AD 生物标志物（包括血浆 Aβ42、Aβ40 和 t-tau）联合使用时，FABP1/Aβ42 和 FABP1/t-tau 均显示出比单独使用这些生物标志物更好的诊断效能。在所有 AUC 分析中，血浆 FABP1/t-tau 和 Aβ42 的组合具有最高的诊断价值（AUC=0.8075，p<0.0001）。