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

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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.