The distinct effect between Amyloid β (1‒40) and Amyloid β (1‒42) on the TRAP-stimulated platelet activation in diabetes mellitus

Amyloid β (Aβ) (1‒40) is the major form in amyloid plaques, while Aβ (1‒42) is predominant in neuronal plaques. Anti-Aβ antibodies are clinically accepted for Alzheimer's disease treatment to remove Aβ from neuronal plaques; however, increase of intracranial hemorrhagic risk is a major concern. We reported that Aβ (1‒40) inhibits thrombin receptor-activating protein (TRAP)-induced platelet activation in healthy volunteers, and the responsiveness of Aβ (1‒40) to the platelet activation is related to brain atrophy in diabetes mellitus (DM) patients. We investigated the difference between the effects of Aβ (1‒40) and Aβ (1‒42) on the platelet activation in DM participants. Both isoforms suppressed the platelet aggregation, but the effect of Aβ (1‒42) was smaller than Aβ (1‒40). The effect of Aβ (1‒42) on the TRAP-stimulated phosphorylation of p38 mitogen-activated protein kinase and stress-activated protein kinase/c-Jun N-terminal kinase was smaller than Aβ (1‒40). Although the differences were not clarified, the effective ratio of Aβ (1‒40) to Aβ (1‒42) on the PDGF-AB secretion effect was related to the ratio on the aggregation and the phosphorylated-HSP27 secretion. These results suggest that the difference of the effects exists between Aβ (1‒40) and Aβ (1‒42) on the TRAP-stimulated platelet activation individually in the DM patients.