Quantitative Neuroimaging Laboratory, Brain Health Imaging Institute, Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
J Alzheimers Dis. 2021;83(1):407-421. doi: 10.3233/JAD-210419.
While amyloid-β (Aβ) plaques and tau tangles are the well-recognized pathologies of Alzheimer's disease (AD), they are more often observed in healthy individuals than in AD patients. This discrepancy makes it extremely challenging to utilize these two proteinopathies as reliable biomarkers for the early detection as well as later diagnosis of AD.
We hypothesize and provide preliminary evidence that topographically overlapping Aβ and tau within the default mode network (DMN) play more critical roles in the underlying pathophysiology of AD than each of the tau and/or Aβ pathologies alone.
We used our newly developed quantification methods and publicly available neuroimaging data from 303 individuals to provide preliminary evidence of our hypothesis.
We first showed that the probability of observing overlapping Aβ and tau is significantly higher within than outside the DMN. We then showed evidence that using Aβ and tau overlap can increase the reliability of the prediction of healthy individuals converting to mild cognitive impairment (MCI) and to a lesser degree converting from MCI to AD. Finally, we provided evidence that while the initial accumulations of Aβ and tau seems to be started independently in the healthy participants, the accumulations of the two pathologies interact in the MCI and AD groups.
These findings shed some light on the complex pathophysiology of AD and suggest that overlapping Aβ and tau pathologies within the DMN might be a more reliable biomarker of AD for early detection and later diagnosis of the disease.
虽然淀粉样蛋白-β（Aβ）斑块和 tau 缠结是阿尔茨海默病（AD）的公认病理学特征，但它们在健康个体中的出现频率高于 AD 患者。这种差异使得将这两种蛋白病理作为 AD 的早期检测以及后期诊断的可靠生物标志物变得极具挑战性。
我们假设并提供初步证据表明，默认模式网络（DMN）内重叠的 Aβ 和 tau 在 AD 的潜在病理生理学中比单独的 tau 和/或 Aβ 病理学发挥更关键的作用。
我们使用新开发的定量方法和来自 303 个人的公开神经影像学数据提供了我们假设的初步证据。
我们首先表明，在 DMN 内观察到重叠的 Aβ 和 tau 的概率明显高于 DMN 之外。然后我们提供了证据表明，使用 Aβ 和 tau 重叠可以提高预测健康个体从正常认知到轻度认知障碍（MCI）以及从 MCI 到 AD 转变的可靠性。最后，我们提供的证据表明，尽管 Aβ 和 tau 的初始积累在健康参与者中似乎是独立开始的，但在 MCI 和 AD 组中，两种病理的积累会相互作用。
这些发现为 AD 的复杂病理生理学提供了一些启示，并表明 DMN 内重叠的 Aβ 和 tau 病理学可能是 AD 的更可靠的早期检测和后期诊断生物标志物。
