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.

项目总结/摘要： β淀粉样蛋白（Aβ）是阿尔茨海默病（AD）的标志，也影响帕金森病（PD） 患者，特别是在晚期阶段，然后痴呆症（PDD）开始发展。然后PDD前进，关于 50%的PDD患者出现与AD相似的非常广泛的神经病理学。它包括错误折叠的Aβ 斑块和tau神经元缠结，而Aβ产生损伤的来源和规模，以及其影响 PDD的发展是未知的。血管周围也有不溶性Aβ淀粉样蛋白的积聚 53%的PD患者存在脑淀粉样血管病（CAA）。我们以前发现系统性Aβ 在脑血栓形成期间由血小板产生的肽，在脑组织上及其周围高度可见。 大脑中的血管此外，在PD的小鼠模型中，然后将化学物质注射到大脑中， 血管壁及周围也出现Aβ，以杀死多巴胺能神经元。我们假设 帕金森病中Aβ和CAA的组织蓄积可能是血小板持续活化的结果 由于局部脑炎症，大量Aβ通过血管壁转运至脑 本研究的目的是寻找血小板相关的机制， 晚期PD发病机制。我们的具体目标将测试是否直接减少血小板计数，血小板 活化/脱颗粒或血浆Aβ载体在Aβ的发展中很重要 积累我们提出的创新研究将表明这种直接方法是否有效， 因此可能导致PD中晚期Aβ积聚的治愈。这种方法可能会打开大门， 新的治疗方法来阻止PDD的发展，这将是一个非常重要的贡献， 一般健康。