Platelet as a physiological model to investigate apoptotic mechanisms in Alzheimer β-amyloid peptide production

Tiziana Casoli, Giuseppina Di Stefano, Belinda Giorgetti, Marta Balietti, Rina Recchioni, Fausto Moroni, Fiorella Marcheselli, Gianni Bernardini, Patrizia Fattoretti, Carlo Bertoni-Freddari

Research output: Contribution to journalArticlepeer-review

Abstract

Although neuronal apoptosis in Alzheimer's disease is generally interpreted as the consequence of the toxicity of extracellular β-amyloid (Aβ) peptide aggregates, some experimental results provide evidence that the Aβ overproduction can be the result of a primary neuronal degeneration. As platelets are considered a good model where to study proteolytic processing of the amyloid precursor protein (APP), we exposed platelets to the proapoptotic agent ionomycin and analyzed Aβ40 and Aβ42 levels in the intracellular and extracellular compartments. The activation of apoptotic pathways in platelets has been verified by mitochondrial membrane depolarization, exposure of phosphatidylserine, protease activation and morphological changes. A significative increase in intraplatelet Aβ40, but not Aβ42, was observed after 10 min treatment with ionomycin. Thus, the activation of apoptotic pathways in platelets determines an altered processing of APP leading to elevated levels of intracellular Aβ40. The specific intracellular production of Aβ40 represents a potential threat to the cells since very high local Aβ40 concentration increases the risk of its aggregation and toxicity. As a result, Aβ40 might be dangerous even before it becomes secreted rendering neurons highly vulnerable.

Original languageEnglish
Pages (from-to)154-162
Number of pages9
JournalMechanisms of Ageing and Development
Volume129
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • β-Amyloid
  • Alzheimer's disease
  • Apoptosis
  • Ionomycin
  • Platelets

ASJC Scopus subject areas

  • Ageing
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

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