The 2018 National Institute on Aging and the Alzheimer's Association (NIA‐AA) research framework recently redefined Alzheimer's disease (AD) as a biological construct, based on in vivo biomarkers reflecting key neuropathologic features. Combinations of normal/abnormal levels of three biomarker categories, based on single thresholds, form the AD signature profile that defines the biological disease state as a continuum, independent of clinical symptomatology. While single thresholds may be useful in defining the biological signature profile, we provide evidence that their use in studies with cognitive outcomes merits further consideration. Using data from the Alzheimer's Disease Neuroimaging Initiative with a focus on cortical amyloid binding, we discuss the limitations of applying the biological definition of disease status as a tool to define the increased likelihood of the onset of the Alzheimer's clinical syndrome and the effects that this may have on trial study design. We also suggest potential research objectives going forward and what the related data requirements would be.

中文翻译：

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观点：阿尔茨海默病生物标志物二分法的临床相关性：是否应该存在“灰色地带”？

2018 年美国国家老龄化研究所和阿尔茨海默病协会 (NIA-AA) 研究框架最近根据反映关键神经病理学特征的体内生物标志物，将阿尔茨海默病 (AD) 重新定义为一种生物学结构。三个生物标志物类别的正常/异常水平的组合，基于单个阈值，形成 AD 特征谱，将生物疾病状态定义为一个连续体，独立于临床症状。虽然单个阈值可能有助于定义生物特征谱，但我们提供的证据表明，它们在具有认知结果的研究中的使用值得进一步考虑。使用来自阿尔茨海默病神经影像学计划的数据，重点是皮质淀粉样蛋白结合，我们讨论了应用疾病状态的生物学定义作为定义阿尔茨海默病临床综合征发病可能性增加的工具的局限性以及这可能对试验研究设计产生的影响。我们还建议未来的潜在研究目标以及相关数据要求是什么。