摘要
阿尔茨海默病(AD)的生物标志物在血液中含量可能因种族、老年性疾病与各种环境风险因素等不同而存在差异,尚缺乏系统性的研究来评估AD生物标志物在中国老年及AD患者人群中的变化以及是否具有准确预测脑内淀粉样蛋白沉积的能力.本工作为一项多中心纵向队列研究,共纳入来自全国各地6个不同临床中心的817个血液样本.研究测量了多个国际上通用的AD生物标志物,包括β-淀粉样蛋白40与42、磷酸化Tau(pTau)蛋白、总Tau蛋白、神经纤维丝轻链(NFL)和胶质纤维酸性蛋白(GFAP),并使用淀粉样斑块PET示踪剂和核磁结构影像对受试者进行综合评估.研究发现,APOE基因型与血浆pTau或血清GFAP组合的预测模型对脑内淀粉样斑块的沉积状态具有较好的区分能力.此外,研究还发现GFAP基线水平越高的患者其神经退行性变的速度越快.本研究结果基于多中心数据,论证了AD血液生物标志物在中国汉族人群中的实用性和应用前景,提示了血液pTau和GFAP是检测AD早期症状的有效指标,为我国AD的早期诊断和治疗提供了参考.
Discrepancies in diagnostic biomarkers for Alzheimer's Disease(AD)may arise from racial disparities,risk factors,or lifestyle differences.Moreover,there has been a lack of systematic and multicenter studies to evaluate baselines of the AD biomarkers in Chinese populations.Thus,there is an urgent need for research to investigate the effectiveness of blood biomarkers for AD,specifically in the Chinese Han population,using a multicenter approach.In the present multicenter-based cross-sectional and longitudinal study,we evaluated 817 blood samples from 6 different clinical centers.We measured plasma amyloid beta(Aβ)-40,Aβ42,phosphorylated tau 181(pTau),total tau(tTau),serum neurofilament light(NFL),and glial fibrillary acidic protein(GFAP).Additionally,~(18)F-florbetapir positron electron tomography and magnetic resonance imaging were also performed.A combination of the APOE genotype with plasma pTau and serum GFAP demonstrated exceptional performance in distinguishing Aβstatus.Furthermore,baseline GFAP levels exhibited a strong association with cognitive decline over time and brain atrophy,with higher GFAP levels predicting a faster rate of neurodegeneration.In summary,these results validate the practicality of blood biomarkers in the Chinese Han population,encompassing various regions within China.Additionally,they emphasize the potential of pTau and GFAP as non-invasive methods for detecting and screening AD at an early stage.
作者
高峰
戴林斌
王琼
刘畅
邓克学
程昭昭
吕心怡
吴燕
张子伊
陶青青
袁晶
李世平
王越
苏娅
程忻
倪俊
吴志英
张舒婷
施炯
申勇
China Aging and Neurodegenerative Initiative(CANDI)Consortium
Feng Gao;Linbin Dai;Qiong Wang;Chang Liu;Kexue Deng;Zhaozhao Cheng;Xinyi Lv;Yan Wu;Ziyi Zhang;Qingqing Tao;Jing Yuan;Shiping Li;Yue Wang;Ya Su;Xin Cheng;Jun Ni;Zhiying Wu;Shuting Zhang;Jiong Shi;Yong Shen;China Aging and Neurodegenerative Initiative(CANDI)Consortium(Department of Neurology,Institute on Aging and Brain Disorders,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China;Neurodegenerative Disorder Research Center,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China;Department of Radiology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China;Department of Neurology,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Neurology and Research Center of Neurology,Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China;Department of Neurology,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100006,China;Department of Neurology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Neurology,National Clinical Research Center for Aging and Medicine,Huashan Hospital,Fudan University,Shanghai 200040,China;Anhui Province Key Laboratory of Biomedical Aging Research,University of Science and Technology of China,Hefei 230001,China;不详)
基金
supported by the National Key Plan for Scientific Research and Development of China(2020YFA0509304 and 2021YFA0805300)
the Chinese Academy of Sciences(XDB39000000)
the National Natural Science Foundation of China(82030034,32121002,and 81971123)
CAMS Innovation Fund for Medical Sciences(2021-I2M-C&T-B-012)
the Fundamental Research Funds for the Central Universities(YD9110002027)
the Guangzhou Key Research Program on Brain Science(202007030008)。
