机构:[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China神经科系统神经内科首都医科大学宣武医院神经疾病高创中心(北京学者工作室)科技平台[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Capital Medical University, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
BackgroundThere is an urgent need for cost-effective, easy-to-measure biomarkers to identify subjects who will develop Alzheimer's disease (AD), especially at the pre-symptomatic stage. This stage can be determined in autosomal dominant AD (ADAD) which offers the opportunity to observe the dynamic biomarker changes during the life-course of AD stages. This study aimed to investigate serum biomarkers during different AD stages and potential novel protein biomarkers of presymptomatic AD. MethodsIn the first stage, 32 individuals [20 mutation carriers including 10 with AD, and 10 with mild cognitive impairment (MCI), and 12 healthy controls] from ADAD families were analyzed. All subjects underwent a complete clinical evaluation and a comprehensive neuropsychological battery. Serum samples were collected from all subjects, and antibody arrays were used to analyze 170 proteins in these samples. The most promising biomarkers were identified during this screening and were then measured in serum samples of 12 subjects with pre-MCI and 20 controls. ResultsThe serum levels of 13 proteins were significantly different in patients with AD or MCI compared to controls. Of the 13 proteins, cathepsin D, immunoglobulin E, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9 (MMP-9), von Willebrand factor (vWF), haptoglobin, and phosphorylated Tau-181 (p-Tau181) correlated with all cognitive measures (R-2 = -0.69-0.76). The areas under the receiver operating characteristic curve of these seven proteins were 0.71-0.93 for the classification of AD and 0.57-0.95 for the classification of MCI. Higher levels of p-Tau181 were found in the serum of pre-MCI subjects than in the serum of controls. The p-Tau181 serum level might detect AD before symptoms occur (area under the curve 0.85, sensitivity 75%, specificity 81.67%). ConclusionsA total of 13 serum proteins showed significant differences between subjects with AD and MCI and healthy controls. The p-Tau181 serum level might be a broadly available and cost-effective biomarker to identify individuals with preclinical AD and assess the severity of AD.
基金:
Key Project of the National Natural Science Foundation of China [81530036, U20A20354]; Beijing Natural Science Foundation [7192077]; National Key R&D Program of China [2017YFC1310100, 2016YFC1306305]; National Key Scientific Instrument and Equipment Development Project [31627803]; Beijing Brain Initiative from Beijing Municipal Science & Technology Commission [Z201100005520016, Z201100005520017]
第一作者机构:[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
通讯作者:
通讯机构:[1]Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China[2]Beijing Key Laboratory of Geriatric Cognitive Disorders, Capital Medical University, Beijing, China[3]Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, China[4]Center of Alzheimer’s Disease, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714):
Qin Wei,Li Fangyu,Jia Longfei,et al.Phosphorylated Tau 181 Serum Levels Predict Alzheimer's Disease in the Preclinical Stage[J].FRONTIERS IN AGING NEUROSCIENCE.2022,14:doi:10.3389/fnagi.2022.900773.
APA:
Qin, Wei,Li, Fangyu,Jia, Longfei,Wang, Qi,Li, Ying...&Jia, Jianping.(2022).Phosphorylated Tau 181 Serum Levels Predict Alzheimer's Disease in the Preclinical Stage.FRONTIERS IN AGING NEUROSCIENCE,14,
MLA:
Qin, Wei,et al."Phosphorylated Tau 181 Serum Levels Predict Alzheimer's Disease in the Preclinical Stage".FRONTIERS IN AGING NEUROSCIENCE 14.(2022)