Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β and misfolded tau proteins causing synaptic dysfunction, and progressive neurodegeneration and cognitive decline. Altered neural oscillations have been consistently demonstrated in AD. However, the trajectories of abnormal neural oscillations in AD progression and their relationship to neurodegeneration and cognitive decline are unknown. Here, we deployed robust event-based sequencing models (EBMs) to investigate the trajectories of long-range and local neural synchrony across AD stages, estimated from resting-state magnetoencephalography. The increases in neural synchrony in the delta-theta band and the decreases in the alpha and beta bands showed progressive changes throughout the stages of the EBM. Decreases in alpha and beta band synchrony preceded both neurodegeneration and cognitive decline, indicating that frequency-specific neuronal synchrony abnormalities are early manifestations of AD pathophysiology. The long-range synchrony effects were greater than the local synchrony, indicating a greater sensitivity of connectivity metrics involving multiple regions of the brain. These results demonstrate the evolution of functional neuronal deficits along the sequence of AD progression.

中文翻译：

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阿尔茨海默病进展的神经生理学轨迹

阿尔茨海默病 (AD) 的特点是β淀粉样蛋白和错误折叠的 tau 蛋白积累，导致突触功能障碍、进行性神经退行性变和认知能力下降。 AD 中神经振荡的改变已得到一致证实。然而，AD 进展过程中异常神经振荡的轨迹及其与神经退行性变和认知能力下降的关系尚不清楚。在这里，我们部署了强大的基于事件的测序模型（EBM）来研究 AD 阶段的远程和局部神经同步轨迹，并根据静息态脑磁图进行估计。 δ-θ 频带神经同步性的增加以及 α 和 β 频带的减少显示了 EBM 整个阶段的渐进变化。 α 和 β 频带同步性的降低先于神经变性和认知能力下降，表明频率特异性神经元同步异常是 AD 病理生理学的早期表现。远程同步效应大于局部同步效应，表明涉及大脑多个区域的连接指标具有更高的敏感性。这些结果证明了功能性神经元缺陷沿着 AD 进展的顺序演变。