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

帕金森病患者大脑中β-淀粉样蛋白的积累

• 批准号: 10843544
• 负责人: MIKHAIL INYUSHIN
• 金额: $ 9.36万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10843544
• 关键词: Abeta synthesis; Affect; Alzheimer' s Disease; American; Amyloid; Amyloid beta-Protein; Amyloidosis; Antiplatelet Drugs; Apolipoproteins; Area; Autoimmunity; Biochemistry; Biology; Blood; Blood Platelets; Blood Vessels; Brain; Brain Neoplasms; Cells; Cerebral Amyloid Angiopathy; Cerebral Thrombosis; Cerebrovascular system; Cerebrum; Chemicals; Coagulation Process; Collaborations; Corpus striatum structure; Data; Dementia; Development; Direct Costs; Disasters; Disease; Disease model; Dopamine; Encephalitis; Facilities and Administrative Costs; Goals; Hour; Immunofluorescence Immunologic; Impaired cognition; Income; Infectious Agent; Inflammation; Injury; Lead; Lesion; Membrane; Midbrain structure; Mus; Natural Immunity; Neurofibrillary Tangles; Oxidopamine; Parkinson Disease; Parkinson' s Dementia; Pathogenesis; Patients; Peptides; Physiology; Plasma; Platelet Activation; Platelet Count measurement; Prealbumin; Process; Production; Public Health; Publishing; Qualifying; Research; Role; Senile Plaques; Site; Skin; Slice; Social Security; Source; Specialist; Substantia nigra structure; Testing; Therapeutic; Thrombosis; Time; Tissues; United States; abeta accumulation; abeta oligomer; antimicrobial; antimicrobial drug; artery occlusion; brain cell; brain tissue; density; disabling symptom; dopaminergic neuron; experience; experimental study; frontal lobe; immunocytochemistry; innovation; meter; motor impairment; mouse model; natural antimicrobial; neuropathology; novel strategies; novel therapeutics; payment; synucleinopathy; tau aggregation; thrombotic

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.

项目总结/摘要： β淀粉样蛋白（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PD痴呆（PDD）开始发展的后期阶段。当PDD进展时，关于 50%的PDD患者出现与AD相似的广泛神经病理学。这包括错误折叠的Aβ斑块 而Aβ-产生损伤的来源、程度及其对PDD的影响 发展未知。在53%的PD患者中，还存在不溶性Aβ淀粉样蛋白的积聚 血管周围，称为脑淀粉样血管病（CAA）。我们以前发现， 脑血栓形成过程中血小板产生的Aβ肽，在脑血栓形成过程中， 大脑中的血管。此外，在PD的鼠模型中，当将化学品注射到PD的小鼠模型中时， 大脑杀死多巴胺能神经元，Aβ出现在血管壁上和周围。我们假设 PD患者组织中Aβ和CAA的蓄积可能是由于局部炎症引起血小板持续活化的结果， 脑炎症，大量Aβ通过血管壁转运到脑组织， 造成伤害。本研究的目的是寻找血小板相关的机制参与晚期- 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决定这种直接方法是否有效 从而可能治愈PD中晚期Aβ积聚。这种方法可能会开辟道路， 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， 公共卫生