PB1401 - Impact of platelet activation on tau protein

Background: Platelet dysfunction is associated with several neurodegenerative disorders including Alzheimer's disease (AD). AD is a progressive neurodegenerative disease. The pathological hallmarks of AD are the accumulation and aggregation of amyloid β (Aβ) peptides in brain tissue, neuroinflammation and hyperphosphorylation of tau protein resulting in the formation of intracellular neurofibrillary tangles in neurons. Platelets exist in a pre-activated state in the blood of AD patients and contain an altered ratio high molecular weight (HMW) to low molecular weight of tau compared to healthy controls, which correlates with specific regional brain atrophy. To date, it is not known whether platelet-derived tau contributes to neuronal damage in AD.

Aims: Identifying the role of platelet-derived tau in AD

Methods: Immunofluorescence staining, immunoblotting and flow cytometry

Results: Analysis of brain tissues from a transgenic mouse model of AD (APP23) demonstrated that platelets are able to migrate into the brain parenchyma where they might interact with neurons. Moreover, platelet activation led to cleavage and phosphorylation of platelet-derived tau. In addition, activation of platelets led to the release of tau. Furthermore, platelet activation by collagen and Aβ40 contributes to mitochondrial dysfunction and ROS generation that might trigger tau aggregation.

Conclusion(s): Taken together, platelet activation leads to release, cleavage and phosphorylation of platelet tau and might contribute to self-aggregation of tau.