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

帕金森病患者大脑中β-淀粉样蛋白的积累-补充剂

• 批准号: 10756300
• 负责人: MIKHAIL INYUSHIN
• 金额: $ 2.35万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756300
• 关键词: Affect; Alzheimer' s Disease; American; Amyloid; Amyloid beta-Protein; Blood; Blood Platelets; Blood Vessels; Brain; Cerebral Amyloid Angiopathy; Cerebral Thrombosis; Chemicals; Dementia; Development; Direct Costs; Disasters; Disease; Encephalitis; Facilities and Administrative Costs; Health; Income; Lead; Parkinson Disease; Parkinson' s Dementia; Pathogenesis; Patients; Peptides; Plasma; Platelet Activation; Platelet Count measurement; Production; Public Health; Research; Research Project Grants; Senile Plaques; Social Security; Source; Testing; Tissues; United States; abeta accumulation; brain tissue; dopaminergic neuron; innovation; mouse model; neuropathology; novel therapeutics; payment; tau aggregation

PROJECT SUMMARY/ABSTRACT: Amyloid beta (Aβ) is the hallmark of Alzheimer’s disease (AD), but also affect Parkinson disease (PD) patients, especially in late stages then the dementia (PDD) start to develop. Then PDD advances, about 50% of PDD patients develop very extensive neuropathology similar to AD. It includes misfolded Aβ plaques and tau neurofibrillary tangles, while the source and scale of Aβ-produced damage, and its effects on PDD development is unknown. There is also accumulation of insoluble Aβ amyloid around blood vessels in 53% PD patients called 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 inside the brain. In addition, in murine model of PD then chemicals are injected in the brain to kill dopaminergic neurons, Aβ appeared on blood vessels walls and around as well. We hypothesized that tissue accumulation of Aβ and CAA in Parkinson disease may be a result of constant platelet activation due to local brain inflammation, with high quantities of Aβ transported through blood vessel walls to brain tissue, injuring it. 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 show 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 gateway for new therapeutics to stop the development of PDD, which would be a very significant contribution to general health.

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，特别是在痴呆(PDD)开始发展的晚期。然后PDD前进，大约 50%的PDD患者发展为非常广泛的类似AD的神经病理。它包括折叠错误的Aβ 斑块和tau神经原纤维缠结，同时对β的来源和规模产生损害，及其影响 关于PDD的开发还不得而知。血管周围也有不溶的A-β淀粉样蛋白积聚。 53%的帕金森病患者称为脑淀粉样血管病(CAA)。我们之前发现系统性Aβ 在脑血栓形成过程中由血小板产生的多肽，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，随后向大脑中注射化学物质 为了杀死多巴胺能神经元，血管壁和周围也出现了β。我们假设 帕金森病患者A-β和CAA的组织积聚可能是由于持续的血小板活化所致 由于局部脑部炎症，大量的Aβ通过血管壁输送到大脑 组织，伤害它。这项建议的目的是找出与血小板相关的机制 晚期帕金森病发病机制。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表明这种直接方法是否有效，以及 从而可以治愈帕金森病晚期A期β积聚。这种方法可能会打开大门 对于新的治疗方法来阻止PDD的发展，这将是对 总体健康状况。