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.

项目摘要/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，尤其是在 PD 痴呆 (PDD) 开始发展的后期阶段，当 PDD 进展时，大约。 50% 的 PDD 患者会出现与 AD 类似的广泛神经病理学，其中包括错误折叠的 Aβ 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对 PDD 的影响 53% 的 PD 患者还存在不溶性 Aβ 淀粉样蛋白的积累。 我们之前发现，血管周围的淀粉样血管病（CAA）是全身性的。 Aβ肽是脑血栓形成过程中血小板产生的，在大脑周围和周围高度可见。 此外，在PD小鼠模型中，当化学物质被注射到大脑内的血管中时。 Aβ 出现在血管壁上和周围。 PD 中 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 Aβ 通过血管壁转运至脑组织， 该提案的目的是找到参与晚期损伤的血小板相关机制。 我们的具体目的将测试血小板计数是否直接减少、血小板减少。 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决定这种直接方法是否有效。 从而可能治愈 PD 晚期 Aβ 积累。 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 公共卫生。