Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, United States.
Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, United States.
Neuroimage. 2021 Feb 15;227:117676. doi: 10.1016/j.neuroimage.2020.117676. Epub 2020 Dec 24.
Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease.
In a cohort of 335 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity.
Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 7-8 years before Aβ-positivity. Temporoparietal tau PET showed increases 4-5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 4-6 years before Aβ-positivity.
Increases in tau and cognitive dysfunction occur years before commonly used thresholds for Aβ-positivity. Explicit estimates of the time for these events provide a clearer picture of the time-course of the amyloid cascade and identify potential windows for specific treatments.
估计阿尔茨海默病关键病理标志物扩散和认知功能障碍发作的时间进程。
在认知功能不同的 335 名老年人队列中，我们根据 Aβ 阳性时间估计了 Aβ、tau 和认知下降的初始变化时间。
脑脊液 Aβ42 和区域性 Aβ PET 变化的小效应量估计在 Aβ 阳性前几十年就发生了。脑脊液 tau 的增加发生在 Aβ 阳性前 7-8 年。颞顶叶 tau PET 显示在 Aβ 阳性前 4-5 年增加。在 Aβ 阳性前 4-6 年就观察到了轻微的认知功能障碍。
tau 的增加和认知功能障碍发生在 Aβ 阳性常用阈值之前数年。这些事件时间的明确估计提供了淀粉样蛋白级联的时间进程更清晰的画面，并确定了特定治疗的潜在窗口期。
