Relationship between the Responsiveness of Amyloid Protein to Platelet Activation by TRAP Stimulation and Brain Atrophy in Patients with Diabetes Mellitus

Type 2 DM is a risk factor for dementia, including Alzheimer's disease (AD), and is associated with brain atrophy. Amyloid beta protein (A beta) deposition in the brain parenchyma is implicated in the neurodegeneration that occurs in AD. Platelets, known as abundant storage of A beta, are recognized to play important roles in the onset and progression of AD. We recently showed that A beta negatively regulates platelet activation induced by thrombin receptor-activating protein (TRAP) in healthy people. In the present study, we investigated the effects of A beta on the TRAP-stimulated platelet activation in DM patients, and the relationship between the individual responsiveness to A beta and quantitative findings of MRI, the volume of white matter hyperintensity (WMH)/intracranial volume (IC) and the volume of parenchyma (PAR)/IC. In some DM patients, A beta reduced platelet aggregation induced by TRAP, while in others it was unchanged or rather enhanced. The TRAP-induced levels of phosphorylated-Akt and phosphorylated-HSP27, the levels of PDGF-AB and the released phosphorylated-HSP27 correlated with the degree of platelet aggregability. The individual levels of not WMH/IC but PAR/IC was correlated with those of TRAP-stimulated PDGF-AB release. Collectively, our results suggest that the reactivity of TRAP-stimulated platelet activation to A beta differs in DM patients from healthy people. The anti-suppressive feature of platelet activation to A beta might be protective for brain atrophy in DM patients.