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: 10652268
• 负责人: MIKHAIL INYUSHIN
• 金额: $ 10.48万
• 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/10652268
• 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.

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