Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Department of Neuropathology, Oxford University Hospitals, Oxford, United Kingdom; and.
J Nucl Med. 2020 Oct;61(10):1413-1418. doi: 10.2967/jnumed.119.230458. Epub 2020 Aug 6.
PET neuroimaging of amyloid-β (Aβ) provides an in vivo biomarker for pathologic changes associated with Alzheimer disease (AD). Aβ-targeted agents have been approved by the Food and Drug Administration, with additional agents, most notably targeting tau, currently under clinical investigation and one approved in May 2020. These agents, along with nonscintigraphic biomarkers from blood and cerebrospinal fluid, have provided an opportunity to investigate the pathogenesis, prodromal changes, and time course of the disease in living individuals. The current understanding is that the neuropathologic changes of the AD continuum begin up to 25 y before the onset of clinical symptomatology. The opportunities afforded by in vivo biomarkers of AD, whether by serum, cerebrospinal fluid examination or PET, have transformed the design of AD therapeutic trials by shifting focus to the preclinical stages of disease. Future disease-modifying therapies, should they be forthcoming, will rely heavily on the use of approved biomarkers or biomarkers currently under investigation to confirm the presence of target pathology. Understanding the progressive neuropathologic changes that occur in AD-and how scintigraphic findings relate to these changes-will help the interpreting physician to fully appreciate the implications of the scintigraphic findings and provide a basis to interpret the examinations. The recently adopted National Institute on Aging-Alzheimer Association guidelines define postmortem AD neuropathologic changes as a composite score based on 3 elements. These elements are the extent of involvement (spread) by cerebral Aβ based on the progression model defined by the Thal Aβ phases, the extent of involvement (spread) by neurofibrillary tangles (composed of hyperphosphorylated tau proteins) based on the progression model defined by Braak, and the Consortium to Establish a Registry for Alzheimer's Disease score, which describes the density of neuritic plaques based on certain key locations in the neocortex. This paper will review the 3 elements that define the National Institute on Aging-Alzheimer's Association scoring system and discusses current evidence on how these elements relate to findings based on Aβ and tau PET scintigraphy.
正电子发射断层扫描（PET）神经影像学可提供与阿尔茨海默病（AD）相关病理变化的体内生物标志物。食品和药物管理局已经批准了针对 Aβ的靶向药物，还有更多的药物，尤其是针对 tau 的药物，目前正在临床研究中，其中一种药物于 2020 年 5 月获得批准。这些药物，以及来自血液和脑脊液的非闪烁生物标志物，为研究 AD 患者体内疾病的发病机制、前驱期变化和病程提供了机会。目前的认识是，AD 连续体的神经病理学变化早在临床症状出现前 25 年就开始了。AD 体内生物标志物（无论是通过血清、脑脊液检查还是 PET）提供的机会改变了 AD 治疗试验的设计，将重点转移到疾病的临床前阶段。如果未来出现疾病修饰疗法，将严重依赖于使用已批准的生物标志物或正在研究中的生物标志物来确认目标病理学的存在。了解 AD 中发生的进行性神经病理学变化，以及闪烁扫描结果与这些变化的关系，将有助于解释医生充分了解闪烁扫描结果的意义，并为解释检查结果提供依据。最近采用的美国国家老龄化研究所-阿尔茨海默病协会指南将死后 AD 神经病理学变化定义为基于 3 个要素的综合评分。这些要素是基于 Thal Aβ 阶段定义的进展模型，大脑 Aβ 的受累程度（传播），由过度磷酸化的 tau 蛋白组成的神经原纤维缠结的受累程度（传播），基于 Braak 定义的进展模型，以及描述基于某些新皮质关键位置的神经原纤维缠结密度的 Consortium to Establish a Registry for Alzheimer's Disease 评分。本文将回顾定义美国国家老龄化研究所-阿尔茨海默病协会评分系统的 3 个要素，并讨论这些要素与基于 Aβ 和 tau PET 闪烁扫描的结果的关系的现有证据。
