Serum GFAP differentiates Alzheimer’s disease from frontotemporal dementia and predicts MCI-to-dementia conversion

失智症 痴呆 内科学 胶质纤维酸性蛋白 胃肠病学 医学 星形胶质增生 阿尔茨海默病 生物标志物 病理 肿瘤科 内分泌学 疾病 化学 中枢神经系统 免疫组织化学 生物化学
作者
Patrick Oeckl,Sarah Anderl‐Straub,Christine A. F. Von Arnim,Inês Baldeiras,Janine Diehl‐Schmid,Timo Grimmer,Steffen Halbgebauer,Anna M. de Kort,Marisa Lima,Tainá M. Marques,Marion Ortner,Isabel Santana,Petra Steinacker,Marcel M. Verbeek,Alexander E. Volk,Albert C. Ludolph,Markus Otto
出处
期刊:Journal of Neurology, Neurosurgery, and Psychiatry [BMJ]
卷期号:93 (6): 659-667 被引量:70
标识
DOI:10.1136/jnnp-2021-328547
摘要

Objective Reactive astrogliosis is a hallmark of Alzheimer’s disease (AD) and frontotemporal dementia (FTD) but differences between the diseases and time course are unclear. Here, we used serum levels of the astroglial marker glial fibrillary acidic protein (GFAP) to investigate differences in patients with AD dementia, mild cognitive impairment (MCI)-AD and behavioural variant FTD (bvFTD). Methods This multicentre study included serum samples from patients diagnosed with AD dementia (n=230), MCI-AD (n=111), bvFTD (n=140) and controls (n=129). A subgroup of patients with MCI-AD (n=32) was longitudinally followed-up for 3.9±2.6 years after sample collection. Serum levels of GFAP, neurofilament light chain (NfL) and pTau181 were measured by Simoa (Quanterix) and Ella (ProteinSimple). Results In total, samples from 610 individuals from four clinical centres were investigated in this study. Serum GFAP levels in AD dementia were increased (median 375 pg/mL, IQR 276–505 pg/mL) compared with controls (167 pg/mL, IQR 108–234 pg/mL) and bvFTD (190 pg/mL, IQR 134–298 pg/mL, p<0.001). GFAP was already increased in the early disease phase (MCI-AD, 300 pg/mL, IQR 232–433 pg/mL, p<0.001) and was higher in patients with MCI-AD who developed dementia during follow-up (360 pg/mL, IQR 253–414 pg/mL vs 215 pg/mL, IQR 111–266 pg/mL, p<0.01, area under the curve (AUC)=0.77). Diagnostic performance of serum GFAP for AD (AUC=0.84, sensitivity 98%, specificity 60%, likelihood ratio 2.5) was comparable to serum pTau181 (AUC=0.89, sensitivity 80%, specificity 87%, likelihood ratio 6.0) but superior to serum NfL (AUC=0.71, sensitivity 92%, specificity 49%, likelihood ratio 1.8). Conclusions Our data indicate a different type of reactive astrogliosis in AD and bvFTD and support serum GFAP as biomarker for differential diagnosis and prediction of MCI-to-dementia conversion.
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