Amyloid beta (Aß) is the hallmark of Alzheimer’s disease (AD), and the dominant concept currently is that an imbalance between the production and clearance of Aß peptides, which are released by brain cells, is the most important factor in the initiation of AD. We previously found that systemic Aß peptide, generated by blood platelets during cerebral thrombosis, is
highly visible around the blood vessels inside the brain in the zone known to be involved in AD. We have also found that Aß disrupts the membrane of fungal cells, working as a pore-forming antibiotic, and is probably involved in antimicrobial defense during thrombosis. We hypothesized that Aß generated by platelets helps to kill microbes but also adds to the Aß produced by neurons and astrocytes, overwhelming the Aß clearance system. AD may develop because of age-related platelet changes, leading to the overproduction of Aß in brain vessels or other causes. The objectives of this proposal are to reduce the Aß overproduction related to platelets and their function and moderate other blood plasma-associated factors influencing the damage from Aß. Our specific aims will test whether the direct reduction of platelet count, platelet activation/degranulation, or blood plasma Aß carriers are important in the initiation and development of AD. Our proposed innovative research will show whether this direct approach is effective and could thereby lead to a cure for AD.
This approach could open the gateway for new therapeutics to stop AD development, which would significantly contribute to general health. Many recent studies suggest that AD develops from systemic protein the same way as other known types of amyloidosis, and our long-term goal is a confirmation (or rejection) of this idea.

SC3GM143983

2022-07-01

2026-06-30