Biomagnetic Imaging Laboratory, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, United States.
Medical Imaging Business Center, Ricoh Company Ltd, Kanazawa, Japan.
Elife. 2024 Mar 28;12:RP91044. doi: 10.7554/eLife.91044.
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.
阿尔茨海默病（AD）的特征是淀粉样β和错误折叠的 tau 蛋白积累，导致突触功能障碍和进行性神经退行性变和认知能力下降。在 AD 中已经一致证明了神经振荡的改变。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），以研究从静息状态脑磁图估计的 AD 各阶段的长程和局部神经同步的轨迹。EBM 各阶段的 delta-theta 波段的神经同步增加，alpha 和 beta 波段的神经同步减少。alpha 和 beta 波段同步的减少先于神经退行性变和认知能力下降，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。长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度量的敏感性更高。这些结果表明，随着 AD 进展序列，功能神经元缺陷不断演变。
