Mastrangelo Andrea, Vacchiano Veria, Zenesini Corrado, Ruggeri Edoardo, Baiardi Simone, Cherici Arianna, Avoni Patrizia, Polischi Barbara, Santoro Francesca, Capellari Sabina, Liguori Rocco, Parchi Piero
Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum Università di Bologna, 40139 Bologna, Italy.
IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.
Int J Mol Sci. 2023 Sep 12;24(18):13976. doi: 10.3390/ijms241813976.
Recent studies reported increased plasma glial acidic fibrillary protein (GFAP) levels in amyotrophic lateral sclerosis (ALS) patients compared to controls. We expanded these findings in a larger cohort, including 156 ALS patients and 48 controls, and investigated the associations of plasma GFAP with clinical variables and other biofluid biomarkers. Plasma GFAP and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers were assessed by the single molecule array and the Lumipulse platforms, respectively. In ALS patients, plasma GFAP was higher than in controls ( < 0.001) and associated with measures of cognitive decline. Twenty ALS patients (12.8%) showed a positive amyloid status (A+), of which nine also exhibited tau pathology (A+T+, namely ALS-AD). ALS-AD patients showed higher plasma GFAP than A- ALS participants ( < 0.001) and controls ( < 0.001), whereas the comparison between A- ALS and controls missed statistical significance ( = 0.07). Plasma GFAP distinguished ALS-AD subjects more accurately (area under the curve (AUC) 0.932 ± 0.027) than plasma p-tau181 (AUC 0.692 ± 0.058, < 0.0001) and plasma neurofilament light chain protein (AUC, 0.548 ± 0.088, < 0.0001). Cognitive measures differed between ALS-AD and other ALS patients. AD co-pathology deeply affects plasma GFAP values in ALS patients. Plasma GFAP is an accurate biomarker for identifying AD co-pathology in ALS, which can influence the cognitive phenotype.
最近的研究报告称，与对照组相比，肌萎缩侧索硬化症（ALS）患者的血浆胶质纤维酸性蛋白（GFAP）水平有所升高。我们在一个更大的队列中扩展了这些发现，该队列包括156例ALS患者和48例对照，并研究了血浆GFAP与临床变量及其他生物流体生物标志物之间的关联。分别通过单分子阵列和Lumipulse平台评估血浆GFAP和阿尔茨海默病（AD）脑脊液（CSF）生物标志物。在ALS患者中，血浆GFAP高于对照组（<0.001），并与认知衰退指标相关。20例ALS患者（12.8%）显示淀粉样蛋白状态为阳性（A+），其中9例还表现出tau病理改变（A+T+，即ALS-AD）。ALS-AD患者的血浆GFAP高于A- ALS参与者（<0.001）和对照组（<0.001），而A- ALS与对照组之间的比较未达到统计学显著性（=0.07）。血浆GFAP比血浆p-tau181（曲线下面积（AUC）0.692±0.058，<0.0001）和血浆神经丝轻链蛋白（AUC 0.548±0.088，<0.0001）更准确地区分ALS-AD受试者（AUC 0.932±0.027）。ALS-AD与其他ALS患者的认知指标存在差异。AD共病理改变深刻影响ALS患者的血浆GFAP值。血浆GFAP是识别ALS中AD共病理改变的准确生物标志物，其可影响认知表型。
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