Crary John F, Trojanowski John Q, Schneider Julie A, Abisambra Jose F, Abner Erin L, Alafuzoff Irina, Arnold Steven E, Attems Johannes, Beach Thomas G, Bigio Eileen H, Cairns Nigel J, Dickson Dennis W, Gearing Marla, Grinberg Lea T, Hof Patrick R, Hyman Bradley T, Jellinger Kurt, Jicha Gregory A, Kovacs Gabor G, Knopman David S, Kofler Julia, Kukull Walter A, Mackenzie Ian R, Masliah Eliezer, McKee Ann, Montine Thomas J, Murray Melissa E, Neltner Janna H, Santa-Maria Ismael, Seeley William W, Serrano-Pozo Alberto, Shelanski Michael L, Stein Thor, Takao Masaki, Thal Dietmar R, Toledo Jonathan B, Troncoso Juan C, Vonsattel Jean Paul, White Charles L, Wisniewski Thomas, Woltjer Randall L, Yamada Masahito, Nelson Peter T
Department of Pathology and Cell Biology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, 10032, USA,
Acta Neuropathol. 2014 Dec;128(6):755-66. doi: 10.1007/s00401-014-1349-0. Epub 2014 Oct 28.
We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (Aβ) plaques. For these "NFT+/Aβ-" brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
我们建议使用一个新术语“原发性年龄相关性tau蛋白病”（PART）来描述一种在老年人脑中普遍观察到的病理状态。许多尸检研究报告称，在没有淀粉样蛋白（Aβ）斑块的情况下，存在与阿尔茨海默病（AD）难以区分的神经原纤维缠结（NFTs）的大脑。对于这些不符合AD神经病理变化正式标准的“NFT+/Aβ-”大脑，NFTs大多局限于内侧颞叶、基底前脑、脑干和嗅觉区域（嗅球和皮质）的结构。PART患者的症状通常从正常到遗忘性认知改变不等，只有少数患者表现出严重损害。由于认知障碍往往较轻，现有的临床病理诊断名称，如“单纯缠结性痴呆”和“以缠结为主的老年性痴呆”，并不精确，不适用于大多数患者。PART在老年个体的尸检中几乎普遍可检测到，但目前在生前无法特异性识别这一病理过程。改进的生物标志物和tau蛋白成像可能在未来使PART在临床环境中得以诊断。事实上，最近的研究已经确定了一种常见的生物标志物特征，包括颞叶萎缩和tau蛋白病，而没有Aβ积累的证据。对于研究人员和临床医生来说，修订后的命名法将提高对这种极其常见的病理变化的认识，同时为未来的研究提供概念基础。我们讨论了先前阐明我们称为PART的病理实体特征的报告，并提出了实用的神经病理学诊断标准。
