Build-up of beta-amyloid in the brain in Parkinson's disease

项目摘要/摘要： 淀粉样β蛋白(Aβ)是阿尔茨海默病(AD)的标志，但也影响帕金森病(PD) 患者，特别是在帕金森氏病痴呆(PDD)开始发展的后期。当PDD前进时，关于 50%的PDD患者出现与AD相似的广泛神经病理。这包括错误折叠的Aβ斑块 和tau神经原纤维缠结，而Aβ损伤的来源和范围及其对PDD的影响 发展是未知的。在53%的帕金森病患者中，也有不溶性A-β淀粉样蛋白积聚 血管周围，称为脑淀粉样血管病(CAA)。我们之前发现系统性的 在脑血栓形成过程中，由血小板产生的一种β多肽在脑血栓及其周围非常明显。 大脑内的血管。此外，在帕金森病小鼠模型中，当化学物质注射到 为了杀死多巴胺能神经元，β出现在血管壁上和周围。我们假设 帕金森病患者Aβ和CAA的组织积聚可能是局部血小板持续活化的结果 脑部炎症，大量的Aβ通过血管壁运输到脑组织， 造成伤害。本研究的目的是寻找晚期高血压患者的血小板相关机制。 帕金森病的发病机制。我们的具体目标将测试是否直接减少了血小板计数，血小板 激活/脱颗粒或血浆Aβ携带者在Aβ的发生中很重要 积累。我们提议的创新研究将决定这种直接方法是否有效 从而可以治愈帕金森病晚期的Aβ积聚。这种方法可能会开辟一条道路 对于新的治疗方法来阻止PDD的发展，这将是对 公共卫生。

PROJECT SUMMARY/ABSTRACT: Amyloid beta (Aβ) is the hallmark of Alzheimer’s disease (AD) but also affects Parkinson’s disease (PD) patients, especially in later stages when PD dementia (PDD) starts to develop. When PDD advances, about 50% of PDD patients develop extensive neuropathology similar to AD. This includes misfolded Aβ plaques and tau neurofibrillary tangles, while the source and scale of Aβ-produced damage and its effects on PDD development are unknown. In 53% of PD patients there is also an accumulation of insoluble Aβ amyloid around blood vessels, known as cerebral amyloid angiopathy (CAA). We previously found that systemic Aβ peptide, generated by blood platelets during cerebral thrombosis, is highly visible on and around the blood vessels within the brain. In addition, in a murine model of PD, when chemicals are injected into the brain to kill dopaminergic neurons, Aβ appears on and around blood vessel walls. We hypothesized that tissue accumulation of Aβ and CAA in PD may be the result of continual platelet activation due to local brain inflammation, with high quantities of Aβ transported through blood vessel walls to brain tissue, causing injury. The objectives of this proposal are to find the platelet-related mechanisms involved in late- PD pathogenesis. Our specific aims will test whether the direct reduction of platelet count, platelet activation/degranulation, or blood plasma Aβ carriers are important in the development of Aβ accumulation. Our proposed innovative research will determine whether this direct approach is effective and could thereby lead to a cure for late-stage Aβ accumulation in PD. This approach might open the way for new therapeutics to stop the development of PDD, which would be a very significant contribution to public health.