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.

项目概要/摘要： β 淀粉样蛋白 (Aβ) 是阿尔茨海默病 (AD) 的标志，但也会影响帕金森病 (PD) 患者，尤其是晚期痴呆症 (PDD) 开始发展，然后 PDD 会进展。 50% 的 PDD 患者会出现与 AD 类似的广泛神经病理学，其中包括 Aβ 错误折叠。 斑块和 tau 神经原纤维缠结，而 Aβ 产生的损伤的来源和规模及其影响 血管周围不溶性 Aβ 淀粉样蛋白的积累对 PDD 发展的影响尚不清楚。 53% 的 PD 患者被称为脑淀粉样血管病 (CAA)，我们之前发现全身性 Aβ。 脑血栓形成过程中血小板产生的肽在脑组织及其周围高度可见。 此外，在PD小鼠模型中，化学物质被注射到大脑内。 为了杀死多巴胺能神经元，Aβ 也出现在血管壁和周围。 帕金森病中 Aβ 和 CAA 的组织积聚可能是血小板持续激活的结果 由于局部脑部炎症，大量 Aβ 通过血管壁转运至大脑 该提案的目的是找到参与其中的血小板相关机制。 晚期PD的发病机制我们的具体目的是检测血小板计数是否直接减少。 活化/脱粒或血浆 Aβ 载体在 Aβ 的发育中很重要 我们提出的创新研究将表明这种直接方法是否有效且有效。 可能会治愈 PD 晚期 Aβ 积聚，从而打开大门。 寻找新的疗法来阻止 PDD 的发展，这将是一个非常重大的贡献 一般健康状况。