Department of Pathology & Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Alzheimers Dement. 2010 May;6(3):230-8. doi: 10.1016/j.jalz.2010.03.008.
Here, we review progress by the Penn Biomarker Core in the Alzheimer's Disease Neuroimaging Initiative (ADNI) toward developing a pathological cerebrospinal fluid (CSF) and plasma biomarker signature for mild Alzheimer's disease (AD) as well as a biomarker profile that predicts conversion of mild cognitive impairment (MCI) and/or normal control subjects to AD. The Penn Biomarker Core also collaborated with other ADNI Cores to integrate data across ADNI to temporally order changes in clinical measures, imaging data, and chemical biomarkers that serve as mileposts and predictors of the conversion of normal control to MCI as well as MCI to AD, and the progression of AD. Initial CSF studies by the ADNI Biomarker Core revealed a pathological CSF biomarker signature of AD defined by the combination of Abeta1-42 and total tau (T-tau) that effectively delineates mild AD in the large multisite prospective clinical investigation conducted in ADNI. This signature appears to predict conversion from MCI to AD. Data fusion efforts across ADNI Cores generated a model for the temporal ordering of AD biomarkers which suggests that Abeta amyloid biomarkers become abnormal first, followed by changes in neurodegenerative biomarkers (CSF tau, F-18 fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging) with the onset of clinical symptoms. The timing of these changes varies in individual patients due to genetic and environmental factors that increase or decrease an individual's resilience in response to progressive accumulations of AD pathologies. Further studies in ADNI will refine this model and render the biomarkers studied in ADNI more applicable to routine diagnosis and to clinical trials of disease modifying therapies.
在这里，我们回顾了宾夕法尼亚生物标志物核心在阿尔茨海默病神经影像学倡议 (ADNI) 中的进展，旨在为轻度阿尔茨海默病 (AD) 开发病理脑脊液 (CSF) 和血浆生物标志物特征，以及预测轻度认知障碍 (MCI) 和/或正常对照受试者向 AD 转化的生物标志物特征。宾夕法尼亚生物标志物核心还与其他 ADNI 核心合作，整合 ADNI 中的数据，以时间顺序排列临床测量、影像学数据和化学生物标志物的变化，这些变化作为正常对照向 MCI 以及 MCI 向 AD 以及 AD 进展的里程碑和预测指标。ADNI 生物标志物核心的初步 CSF 研究揭示了 AD 的病理性 CSF 生物标志物特征，该特征由 Abeta1-42 和总 tau (T-tau) 的组合定义，该特征有效地描绘了 ADNI 中进行的大型多站点前瞻性临床研究中的轻度 AD。该特征似乎可以预测从 MCI 向 AD 的转化。ADNI 核心之间的数据融合努力生成了一个 AD 生物标志物时间顺序的模型，该模型表明 Abeta 淀粉样蛋白生物标志物首先异常，随后神经退行性生物标志物 (CSF tau、F-18 氟脱氧葡萄糖正电子发射断层扫描、磁共振成像) 发生变化，然后出现临床症状。由于增加或减少个体对 AD 病理进行性积累的弹性的遗传和环境因素，这些变化在个体患者中的时间各不相同。ADNI 中的进一步研究将完善该模型，并使 ADNI 中研究的生物标志物更适用于常规诊断和疾病修饰治疗的临床试验。
