Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alzheimers Dement. 2021 May;17(5):822-830. doi: 10.1002/alz.12233. Epub 2020 Nov 23.
The ATN framework provides an in vivo diagnosis of Alzheimer's disease (AD) using cerebrospinal fluid (CSF) biomarkers of pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N). ATN is rarely evaluated in pathologically confirmed patients and its poor sensitivity to suspected non-Alzheimer's pathophysiologies (SNAP), including frontotemporal lobar degeneration (FTLD), leads to misdiagnoses. We compared accuracy of ATN (ATN ) using CSF total tau (t-tau) to a modified strategy (ATN ) using CSF neurofilament light chain (NfL) in an autopsy cohort.
ATN and ATN were trained in an independent sample and validated in autopsy-confirmed AD (n = 67) and FTLD (n = 27).
ATN more accurately identified FTLD as SNAP (sensitivity = 0.93, specificity = 0.94) than ATN (sensitivity = 0.44, specificity = 0.97), even in cases with co-occurring AD and FTLD. ATN misclassified fewer AD and FTLD as "Normal" (2%) than ATN (14%).
ATN is a promising diagnostic strategy that may accurately identify both AD and FTLD, even when pathologies co-occur.
ATN 框架使用病理淀粉样斑块（A）、缠结（T）和神经退行性变（N）的脑脊液（CSF）生物标志物提供阿尔茨海默病（AD）的体内诊断。ATN 在经病理证实的患者中很少进行评估，其对疑似非阿尔茨海默病病理生理学（SNAP）的敏感性差，包括额颞叶变性（FTLD），导致误诊。我们比较了使用脑脊液总 tau（t-tau）的 ATN（ATN）和使用脑脊液神经丝轻链（NfL）的改良策略（ATN）在尸检队列中的准确性。
ATN 和 ATN 在独立样本中进行训练，并在经尸检证实的 AD（n=67）和 FTLD（n=27）中进行验证。
ATN 比 ATN 更准确地将 FTLD 识别为 SNAP（敏感性=0.93，特异性=0.94），即使在 AD 和 FTLD 同时存在的情况下也是如此。ATN 将 AD 和 FTLD 错误分类为“正常”的比例（2%）低于 ATN（14%）。
ATN 是一种很有前途的诊断策略，即使在同时存在多种病理的情况下，也可以准确识别 AD 和 FTLD。
