Release of β-amyloid from high-density platelets: Implications for Alzheimer's disease pathology

Tiziana Casoli, Giuseppina Di Stefano, Belinda Giorgetti, Yessica Grossi, Marta Balietti, Patrizia Fattoretti, Carlo Bertoni-Freddari

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

The main component of Alzheimer's disease (AD) senile plaques in the brain is amyloid-β peptide (Aβ), a proteolytic fragment of the amyloid precursor protein (APP). Platelets contain both APP and Aβ and much evidence suggests that these cells may represent a useful tool to study bothamyloidogenic and nonamyloidogenic pathways of APP processing. It has been demonstrated that platelets activated by physiological agonists, such as thrombin and collagen, specifically secrete Aβ ending at residue 40. To verify whether APP β-processing could be observed also in an in vitro system of highly concentrated platelets, we measured the Aβ released in the incubation media of 5 ± 109 platelets/mL by enzyme-linked immunosorbent assay (ELISA). The activation status of platelets was investigated by ultrastructural analysis. We found that Aβ40 levels were significantly higher in incubation media of 5±109/mL platelets in comparison with 108/mL platelets (normalized values), while Aβ42 levels were not affected by cell density. The ultrastructural analysis showed platelets at different phases of activation: some platelets were at earlier stage, characterized by granule swelling and dilution, others had granules concentrated in a compact mass in the cell centers within constricted rings of circumferential microtubules (later stage). Normally concentrated cells had the characteristic morphology of resting platelets. Our data suggest that high-density platelets undergo activation likely by increased frequency of platelet-platelet collisions. This, in turn, determines the activation of APP β-processing with consequent release of Aβ40. Investigating the biochemical pathways triggering Aβ secretion in platelets might provide important information for developing tools to modulate this phenomenon in AD brains.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages170-178
Number of pages9
Volume1096
DOIs
Publication statusPublished - Jan 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1096
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • β-amyloid
  • Alzheimer's disease
  • Cell density
  • Platelet activation
  • Platelets

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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