Thursday, April 18, 2024
4/18/2024
PROJECT SUMMARY/ABSTRACT: Amyloid beta (Aß) 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 Aß plaques and tau neurofibrillary tangles, while the source and scale of Aß-produced damage and its effects on PDD development are unknown. In 53% of PD patients there is also an accumulation of insoluble Aß amyloid around blood vessels, known as cerebral amyloid angiopathy (CAA). We previously found that systemic Aß 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, Aß appears on and around blood vessel walls. We hypothesized that tissue accumulation of Aß and CAA in PD may be the result of continual platelet activation due to local brain inflammation, with high quantities of Aß 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 Aß carriers are important in the development of Aß accumulation. Our proposed innovative research will determine whether this direct approach is effective and could thereby lead to a cure for late-stage Aß 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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