包含聚合tau蛋白的NFTs是AD典型病理特征之一。最新证据表明，NFTs形成之前的tau蛋白低聚物（O-Tau）在AD早期神经损伤中起关键作用。针对AD脑网络研究现状中病理基础仍不明确这一不足，我们基于O-Tau经突触传播及在AD发病早期对轴突和髓鞘损害的诸多证据提出假设，O-Tau毒性及经突触传播可能是AD脑功能和结构网络属性发生改变的重要病理基础，其随AD病程的时空变化及对神经网络的影响机制亟待阐明。本项目在既往工作上进一步深化，拟以rTg4510转基因AD小鼠为研究对象，通过多模态影像学PET/MRI和组织细胞学的对比研究，从宏观和微观两个角度探讨O-Tau时空变化与髓鞘破坏和轴突损伤以及与脑结构和功能网络破坏的关系，并阐明O-Tau的时空变化对神经网络的影响机制。本项目的完成将为AD神经网络变化的病理基础提供新的依据，对于进一步明确O-Tau在AD发病机制中的作用具有重要意义。

Neurofibrillary tangles (NFTs) containing aggregated tau protein are a pathological hallmark of Alzheimer's disease (AD). Recent evidence indicated that tau oligomers (O-Tau) that precedes NFTs plays a key role in the neuronal dysfunction at an early stage of AD. Considering that the pathological mechanisms of neural network disruption in AD remains unclear, we proposed that O-Tau may be the cause for the disruption of the functional and structure network in AD based on the evidence of its “prion-like” toxicity and propagation, as well as its damage to the axon and myelin sheaths in young tauopathy AD mice. Therefore, it is urgent and necessary to investigate the impact of O-Tau on the neural networks in early AD. In this project, we further evaluated the spatial and temporal evolution of tau, axon and myelin, as well as brain networks quantitatively on rTg4510 transgenic AD mice and controls. By comparing the results of multi-modal imaging study(PET/MRI) and histocytology study, we want to clarity how the progression of O-Tau impacts the neural networks of early AD, and finally certify that the spatial and temporal evolution of O-tau plays a critical role in the disruption of functional and structure network in AD. Completion of this project will add new evidence to the pathological mechanism of AD brain network damage, and further illuminate the core role of O-Tau in the pathogenesis of AD.