Does Vision Loss Affect Tauopathy in the Brain

视力丧失会影响大脑中的Tau病吗 总结 Tau是微管相关蛋白家族的成员，其主要由神经元表达， 特别是在轴突中，它控制着微管的聚合和稳定， 轴突运输Tau病，特征为聚集的和/或 神经元内的过度磷酸化的tau蛋白是阿尔茨海默病（AD）和许多其他疾病的标志。 包括额颞叶痴呆伴帕金森综合征-17（FTDP-17）、皮克病、进行性 核上性麻痹和皮质基底节变性。Tauopathies是最严重的疾病之一， 影响我们快速增长的老龄化人口。由于缺乏有效的诊断、预防手段， 这些疾病严重损害了患者的日常生活，并显著增加了经济成本， 他们、他们的家人和社会。视网膜是大脑神经网络的延伸。它共享 许多类似的病理生理变化和潜在的机制与大脑在神经退行性疾病 疾病包括AD。越来越多的研究人员和临床医生的共识是， 眼睛和大脑可能比我们想象的更复杂而中枢神经系统（CNS）功能障碍 将以不同的方式影响视觉功能，新出现的证据表明，视觉障碍可能 会导致大脑神经退化多个队列临床研究表明， 包括青光眼和白内障在内的疾病会增加患痴呆症和AD的风险， 拔牙与痴呆症发展风险降低显著相关。然而，相互矛盾的研究 保持。考虑到临床研究无法控制年龄等混杂变量， 认知障碍变得明显，视力障碍的程度，这并不奇怪， 报道了相互矛盾的结果，不能确定视力丧失与AD之间的因果关系。 测试.因此，我们建议使用控制良好的动物实验来验证视觉 损伤会加速大脑中的tau蛋白病。我们将使用两种不同的视觉障碍来测试这一假设 对青光眼和白内障中所见的视网膜神经元损伤和视觉剥夺进行建模的模型， 但在更大程度上，我们可以明确地测试视觉之间的关系， 损失和tau蛋白病。本提案与“NOT-AG-21-044”的目标高度一致，即“调查如何 感觉系统的功能变化影响AD的发展和进展”。完成 拟议的研究将提供重要的新知识，填补目前的知识空白， 为通过恢复良好视力预防和治疗tau蛋白病提供科学依据。本项目开发的模型 将作为进一步研究视力丧失引起的机制的基础。 tau蛋白病中的神经变性

Does Vision Loss Affect Tauopathy in the Brain SUMMARY Tau is a member of the microtubule-associated proteins family, which is mainly expressed by neurons, especially in their axons where it controls the polymerization and stabilization of the microtubules and regulates axonal transport. Tauopathies, characterized by abnormal intracellular accumulation of aggregated and/or hyperphosphorylated tau within neurons, is a hallmark of Alzheimer's disease (AD) and a number of other disorders including frontotemporal dementia with parkinsonism-17 (FTDP-17), Pick disease, progressive supranuclear palsy and corticobasal degeneration. Tauopathies are among the most crippling conditions that affect our rapidly growing aging population. Due to the lack of effective diagnostics, preventative means, and treatments, these diseases significantly impair the daily life of patients and markedly impose financial costs to them, their family members and society. The retina is an extension of the neural network of the brain. It shares many similar pathophysiological changes and underlying mechanisms with the brain during neurodegenerative diseases including AD. Growing consensus among researchers and clinicians is that the interdependency of eye and brain maybe more intricate than we thought. While dysfunction of the central nervous system (CNS) will influence visual function in different ways, emerging evidence suggests that visual impairment may contribute to neurodegeneration in the brain. Multiple cohort clinical studies demonstrate that visual-impairment diseases including glaucoma and cataract increase risk of developing dementia and AD, and cataract extraction is significantly associated with lower risk of dementia development. However, conflicting studies remain. Considering clinical studies cannot control for confounding variables such as age, the stage when cognitive impairment becomes noticeable, and the extent of visual impairment, it is not surprising that conflicting results were reported, and a cause-and-effect relationship from vision loss to AD could not be tested. Therefore, we propose to use well-controlled animal experiments to test the hypothesis that visual impairment accelerates tauopathy in the brain. We will test this hypothesis using two distinct visual impairment models that model retinal neuronal injury and visual deprivation as seen in glaucoma and cataract, respectively, but at much severer extents so that we can unambiguously test the relationship between vision loss and tauopathy. This proposal is highly in line with the objectives of “NOT-AG-21-044” to “investigating how functional changes in sensory systems impact the development and progression of AD”. Completion of the proposed studies will provide important new knowledge that will fill the current knowledge gaps and provide scientific base for preventing and treating tauopathy by restoring good vision. Models developed in this project will serve as the foundation for further investigation of mechanisms by which visual loss causes neurodegeneration in tauopathy.