Glial fibrillary acidic protein as a biomarker for diagnosis of Alzheimer’s disease in cerebrospinal fluid, plasma and saliva measured with Lumipulse technology: a narrative review

Josef Marksteiner a, Christian Humpel b 1

a Department of Psychiatry and Psychotherapy A, Hall State Hospital, Hall in Tirol 6060, Austria

b Laboratory of Psychiatry and Experimental Alzheimer’s Research, Medical University of Innsbruck, Austria

Received 10 December 2024, Revised 8 January 2025, Accepted 17 January 2025, Available online 27 January 2025, Version of Record 27 January 2025.

https://doi.org/10.1016/j.neumar.2025.100038

Abstract

Glial fibrillary acidic protein is an intermediate filament protein released primarily by astrocytes in the central nervous system, providing structural and functional support to neurons. Glial fibrillary acidic protein is a key biomarker of neuroinflammation and astrocyte activation. Recent research advances have highlighted the potential of glial fibrillary acidic protein as a diagnostic and prognostic marker for Alzheimer's disease. Traditionally, cerebrospinal fluid has been the primary medium for analyzing biomarkers of neurodegeneration; however, the detection of biomarkers in plasma and saliva may offer new possibilities for non-invasive diagnostic methods, thus providing practical advantages for routine monitoring and early detection. The aim of this narrative review is to describe the differences and significance of the biomarker glial fibrillary acidic protein in plasma, cerebrospinal fluid, and saliva of patients with Alzheimer's disease. Using a novel luminescence-based method, the Lumipulse technology, the article detects and analyzes possible differences in the concentration of glial fibrillary acidic protein in cerebrospinal fluid, blood, and saliva of healthy individuals and patients with Alzheimer's disease. Although elevated glial fibrillary acidic protein levels in the cerebrospinal fluid of patients with Alzheimer's disease may reflect neuroinflammation, the high variability of the samples and the nonsignificant differences in glial fibrillary acidic protein levels, when compared with those of healthy individuals, limit its utility as a diagnostic marker. In contrast, plasma glial fibrillary acidic protein levels were higher in patients with Alzheimer's disease than in healthy subjects, showing a potential as a noninvasive diagnostic marker. Notably, plasma glial fibrillary acidic protein was stable at room temperature for at least 7 days. Salivary glial fibrillary acidic protein levels were close to the detection level, making it unsuitable for use as a biomarker of Alzheimer's disease. The results of this article confirm that plasma glial fibrillary acidic protein can be used as a potential biomarker for the diagnosis of Alzheimer's disease, is stable, and can effectively differentiate between Alzheimer's disease and healthy individuals.

利用 Lumipulse 技术测量血浆、脑脊液和唾液中潜在的阿尔茨海默病生物标志物胶质纤维酸性蛋白：一项叙述性综述

摘要

胶质纤维酸性蛋白是一种中间丝蛋白，主要由中枢神经系统中的星形胶质细胞释放，为神经元提供结构和功能支持。胶质纤维酸性蛋白 是神经炎症和星形胶质细胞活化的关键生物标志物。最近的研究进展突显了 胶质纤维酸性蛋白 作为阿尔茨海默病诊断和预后标志物的潜力。以往脑脊液被认为是分析神经变性生物标志物的主要介质，然而在血浆和唾液中检测生物标志物可能为非侵入性诊断方法提供新的可能性，从而为常规监测和早期检测提供实际优势。此综述的目的是阐述阿尔茨海默病患者血浆、脑脊液和唾液中的生物标志物胶质纤维酸性蛋白的差异和意义。文章使用一种基于发光的新型方法—Lumipulse技术，检测并分析了健康人和阿尔茨海默病患者脑脊液、血液和唾液中胶质纤维酸性蛋白水平的可能差异。结果发现，健康人的脑脊液、血液和唾液中胶质纤维酸性蛋白水平均较低。虽然阿尔茨海默病患者脑脊液中的胶质纤维酸性蛋白水平升高可能反映出阿尔茨海默病患者的神经炎症，但其样本变异性较大，且与健康人相比胶质纤维酸性蛋白水平差异不显著，这限制了其作为诊断标志物的效用。相反，阿尔茨海默病患者血浆中的胶质纤维酸性蛋白水平高于健康人，显示出作为非侵入性诊断标志物的潜力，而且血浆中的 胶质纤维酸性蛋白 在室温下至少可稳定 7 d。而唾液中的胶质纤维酸性蛋白水平则较低且与健康人差异不显著，不适合作为阿尔茨海默病的生物标志物。文章结果证实，血浆胶质纤维酸性蛋白可作为诊断阿尔茨海默病的潜在生物标记物，具有稳定性，可以有效区分阿尔茨海默病和健康人。