AD源性MCI患者血小板候选生物学标志物纵向随访研究

The coexistence of plaques composed of amyloid β (Aβ) and neurofibrillary tangles (NFT) in the brain of patients with Alzheimer’s disease（AD）are the characteristics of neuropathology of AD. The features indicated by Aβ1-42, total tau protein (T-tau), hyperphosphorylated tau protein (P-tau) levels in cerebrospinal fluid (CSF) and molecular-PET imaging are the biomarkers of AD, which has been taken into the standard of AD diagnosis in parallel as "supporting standard of diagnosis." Moreover, based on the changes of CSF biomarkers, mild cognitive impairment (MCI) due to AD (MCI due to AD) has been divided from MCI，and is the highest risk subjects for the development of AD. Unfortunately, it is extremely difficult to get CSF and to finish scanning of PET for MCI patients and population in China. Thereby, the new standard of diagnosis for AD is difficult to be used in clinical practice even research in China. The most recent studies showed that platelets contain amyloid precursor protein (APP) and tau protein，and their changes have been found in the platelets of AD and its spectrum disorders, indicating that key factors of Aβ and tau protein processing pathway in platelets may be regarded as platelets-based biomarkers for AD and “MCI due to AD”. Thereby, the present study will carry to research in “MCI due to AD”subjects first in China. After finishing the assessment of cognitive function and of Event-Related Potentials, the research will complete the measurement of Aβ42, T-tau and P-tau levels in CSF and of APP-r, T-tau, tau-r and P-tau levels in platelets of the patients at baseline and in two years follow up study in the meantime. After comparing each biomarker level and their ratio within the patients group and between the patients and normal subjects, this study will try to clarify the importance and efficacy of biomarkers for early-diagnosis, indicating the degree of cognitive impairment, the progression and conversion of disease. Finally, the study may find platelets-based biomarkers with higher specificity and sensitivity and serve early-screening, early-assessment and early-diagnosis of AD.

阿尔茨海默病（Alzheimer’s disease, AD）两类3种生物学标志物已被作为“支持诊断标准”平行纳入AD最新诊断标准。依据该生物学标志物变化，又从轻度认知损害（mild cognitive impairment, MCI）中划分出“AD源性MCI”，使其成为AD最高危人群。遗憾的是，在中国，脑脊液获取困难重重，分子PET难以推广，新的诊断标准实施困难。研究发现：血小板中存在淀粉样前体蛋白和tau蛋白；初步研究提示：血小板中β-淀粉样蛋白和tau代谢通路关键因子有望作为AD生物学标志物。因此，本课题拟在中国率先入组“AD源性MCI”患者，完成多维度认知功能和多任务ERP测评，同步随访测定脑脊液和血小板中两类生物学标志物，对比分析各标志物在早期诊断、病情严重度、疾病发展和转归中的效能，阐明AD发生发展机制，推动血小板生物学标志物在AD早期筛查诊断的应用。

阿尔茨海默病（Alzheimer’s disease, AD）两类3种生物学标志物已被作为“支持诊断标准”平行纳入AD最新诊断标准。依据该生物学标志物变化，又从轻度认知损害（mild cognitive impairment, MCI）中划分出“AD源性MCI”，使其成为AD最高危人群。遗憾的是，在中国，脑脊液获取困难重重，分子PET难以推广，新的诊断标准实施困难。研究发现：血小板中存在淀粉样前体蛋白和tau蛋白；初步研究提示：血小板中β-淀粉样蛋白和tau代谢通路关键因子有望作为AD生物学标志物。本课题在中国率先入组了“AD源性MCI”患者，完成了多维度认知功能和多任务ERP测评，同步随访测定了脑脊液和血小板中两类生物学标志物，对比分析了各标志物在早期诊断、病情严重度、疾病发展和转归中的效能，阐明了AD发生发展机制，推动了血小板生物学标志物在AD早期筛查诊断的应用。