Douglas Research Centre, McGill University, Montreal, Quebec, Canada.
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Nat Neurosci. 2024 Nov;27(11):2130-2137. doi: 10.1038/s41593-024-01763-8. Epub 2024 Sep 18.
Animal and computational models of Alzheimer's disease (AD) indicate that early amyloid-β (Aβ) deposits drive neurons into a hyperactive regime, and that subsequent tau depositions manifest an opposite, suppressive effect as behavioral deficits emerge. Here we report analogous changes in macroscopic oscillatory neurophysiology in the human brain. We used positron emission tomography and task-free magnetoencephalography to test the effects of Aβ and tau deposition on cortical neurophysiology in 104 cognitively unimpaired older adults with a family history of sporadic AD. In these asymptomatic individuals, we found that Aβ depositions colocalize with accelerated neurophysiological activity. In those also presenting medial-temporal tau pathology, linear mixed effects of Aβ and tau depositions indicate a shift toward slower neurophysiological activity, which was also linked to cognitive decline. We conclude that early Aβ and tau depositions relate synergistically to human cortical neurophysiology and subsequent cognitive decline. Our findings provide insight into the multifaceted neurophysiological mechanisms engaged in the preclinical phases of AD.
阿尔茨海默病（AD）的动物和计算模型表明，早期淀粉样蛋白-β（Aβ）沉积会使神经元进入过度活跃状态，而随后的 tau 沉积则表现出相反的抑制作用，因为行为缺陷出现。在这里，我们报告了人类大脑中宏观振荡神经生理学的类似变化。我们使用正电子发射断层扫描和无任务磁共振成像来测试 104 名认知正常的有家族史的散发性 AD 老年患者的 Aβ 和 tau 沉积对皮质神经生理学的影响。在这些无症状个体中，我们发现 Aβ 沉积与加速的神经生理学活动共定位。在那些也表现出内侧颞叶 tau 病理学的个体中，Aβ 和 tau 沉积的线性混合效应表明向更慢的神经生理学活动转变，这也与认知能力下降有关。我们得出结论，早期 Aβ 和 tau 沉积与人类皮质神经生理学和随后的认知能力下降呈协同关系。我们的研究结果为 AD 临床前阶段涉及的多方面神经生理学机制提供了深入了解。
