近日，加拿大麦吉尔大学Sylvain Baillet研究小组，报道了Aβ和tau病理与无症状老年人皮层神经生理学和认知能力下降的协同关联。相关论文于2024年9月18日发表在《自然—神经科学》杂志上。

研究团队报告了人类大脑宏观振荡神经生理学的类似变化。该研究组使用正电子发射断层扫描（PET）和无任务磁脑电图（MEG），来测试淀粉样蛋白-β（Aβ）和tau沉积对皮质神经生理的影响。研究对象为104名有散发性阿尔茨海默病家族史的认知正常老年人。

在这些无症状的个体中，该课题组人员发现Aβ沉积与加速的神经生理活动共定位。在那些也表现出中颞叶tau病理的患者中，Aβ和tau沉积的线性混合效应表明，神经生理活动向较慢的方向转变，这也与认知能力下降有关。

研究小组得出结论，早期Aβ和tau沉积与人类皮层神经生理学和随后的认知能力下降有协同关系。他们的发现为阿尔茨海默病临床前阶段的，多方面神经生理机制提供了见解。

研究人员表示，阿尔茨海默病（AD）的动物模型和计算模型表明，早期的淀粉样蛋白-β（Aβ）沉积会使神经元进入过度活跃状态，而随后的tau沉积在行为缺陷出现时，表现出相反的抑制效应。

附：英文原文

Title: Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults

Author: Gallego-Rudolf, Jonathan, Wiesman, Alex I., Pichet Binette, Alexa, Villeneuve, Sylvia, Baillet, Sylvain

Issue&Volume: 2024-09-18

Abstract: 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.

DOI: 10.1038/s41593-024-01763-8

Source: https://www.nature.com/articles/s41593-024-01763-8