阿尔茨海默病神经影像学计划2生物标志物核心：进展与计划综述
The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans.
作者信息
Kang Ju-Hee, Korecka Magdalena, Figurski Michal J, Toledo Jon B, Blennow Kaj, Zetterberg Henrik, Waligorska Teresa, Brylska Magdalena, Fields Leona, Shah Nirali, Soares Holly, Dean Robert A, Vanderstichele Hugo, Petersen Ronald C, Aisen Paul S, Saykin Andrew J, Weiner Michael W, Trojanowski John Q, Shaw Leslie M
机构信息
Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pharmacology and Clinical Pharmacology, Hypoxia-Related Disease Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Alzheimers Dement. 2015 Jul;11(7):772-91. doi: 10.1016/j.jalz.2015.05.003.
INTRODUCTION
We describe Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1-42), t-tau, and p-tau181 analytical performance, definition of Alzheimer's disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids.
METHODS
Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1-42, t-tau, and p-tau181 data.
RESULTS
CSF AD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies.
DISCUSSION
Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials.
引言
我们描述了阿尔茨海默病神经影像学倡议（ADNI）生物标志物核心的进展，包括：生物样本库；脑脊液（CSF）淀粉样蛋白β（Aβ1-42）、总tau蛋白（t-tau）和磷酸化tau蛋白181（p-tau181）的分析性能、用于检测斑块的阿尔茨海默病（AD）特征定义、缠结负担以及进展为AD的风险增加；AD疾病异质性；标准化进展；以及使用ADNI生物流体的新研究。
方法
回顾由ADNI生物标志物核心教员撰写或共同撰写的出版物以及选定的非ADNI研究，以加深对CSF Aβ1-42、t-tau和p-tau181数据的理解和解释。
结果
基于对非ADNI在世受试者的CSF研究以及随后AD的尸检确认，使用经过验证的AlzBio3免疫测定法对CSF进行AD生物标志物测量，可在临床前和前驱疾病阶段检测到神经病理学AD特征。由于遗传/环境因素增加或降低了对AD病理的抵抗力，ADNI各核心之间的合作产生了个体间不同的AD生物标志物时间排序模型。
讨论
进一步的研究将完善该模型，并使在ADNI中研究的生物标志物能够在临床和疾病修饰治疗试验中得到应用。
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