ObjectiveA clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD).MethodsResearch participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual. The timing of change for plasma, CSF, imaging, and cognitive measures was calculated by comparing restricted cubic splines of cross‐sectional data from the amyloid PET positive and negative groups.ResultsThe amyloid PET positive sub‐cohort (n = 118) had an average age of 70.4 ± 7.4 years (mean ± standard deviation) and 16% were cognitively impaired. The amyloid PET negative sub‐cohort (n = 277) included individuals with low levels of amyloid plaque burden at all scans who were cognitively unimpaired at the time of the scans. Biomarker changes were detected 15–19 years before estimated symptom onset for CSF Aβ42/Aβ40, plasma Aβ42/Aβ40, CSF pT217/T217, and amyloid PET; 12–14 years before estimated symptom onset for plasma pT217/T217, CSF neurogranin, CSF SNAP‐25, CSF sTREM2, plasma GFAP, and plasma NfL; and 7–9 years before estimated symptom onset for CSF pT205/T205, CSF YKL‐40, hippocampal volumes, and cognitive measures.InterpretationThe use of an amyloid clock enabled visualization and analysis of biomarker changes as a function of estimated years from symptom onset in sporadic AD. This study demonstrates that estimated years from symptom onset based on an amyloid clock can be used as a continuous staging measure for sporadic AD and aligns with findings in autosomal dominant AD. ANN NEUROL 2024

中文翻译：

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散发性阿尔茨海默氏病从症状出现起的估计年内生物标志物变化的时间

目的使用将淀粉样蛋白正电子发射断层扫描 (PET) 与时间相关的时钟来估计散发性阿尔茨海默病 (AD) 中生物标志物变化的时间。方法研究参与者包括在淀粉样蛋白 PET 检测 2 年内接受脑脊液 (CSF) 采集的参与者。估计每个人淀粉样蛋白出现和 AD 症状出现的年龄。通过比较淀粉样蛋白 PET 阳性组和阴性组横截面数据的限制三次样条，计算血浆、脑脊液、影像学和认知测量的变化时间。结果淀粉样蛋白 PET 阳性亚组 (n = 118) 的平均年龄为 70.4 ± 7.4 岁（平均值 ± 标准差），16% 存在认知障碍。淀粉样蛋白 PET 阴性亚组 (n = 277) 包括在所有扫描中淀粉样斑块负荷水平较低且在扫描时认知能力未受损的个体。在估计症状出现前 15-19 年检测到 CSF Aβ42/Aβ40、血浆 Aβ42/Aβ40、CSF pT217/T217 和淀粉样蛋白 PET 的生物标志物变化；血浆 pT217/T217、脑脊液神经粒蛋白、脑脊液 SNAP-25、脑脊液 sTREM2、血浆 GFAP 和血浆 NfL 的估计症状发作前 12-14 年；以及脑脊液 pT205/T205、脑脊液 YKL-40、海马体积和认知测量的估计症状发作前 7-9 年。零星的AD。这项研究表明，根据淀粉样蛋白时钟估计症状出现的年数可用作散发性 AD 的连续分期措施，并与常染色体显性 AD 的研究结果一致。安神经学 2024