Platelets provide human tissue to unravel pathogenic mechanisms of Alzheimer disease

Flaminio Cattabeni, Francesca Colciaghi, Monica Di Luca

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder characterised by a progressive cognitive and memory decline. From a neuropathological point of view, Alzheimer disease is defined by the presence of characteristic lesions, i.e. mature senile plaques, neurofibrillary tangles and amyloid angiopathy. In particular, accumulation of the amyloid β-peptide in the brain parenchyma and vasculature is an invariant event in the pathogenesis of both sporadic and familial Alzheimer cases. Amyloid β-peptide originates from a larger precursor, the Amyloid Precursor Protein (APP) ubiquitously expressed. Among the different peripheral cells expressing APP forms, platelets are particularly interesting since they show concentrations of its isoforms equivalent to those found in brain. Moreover, a number of laboratories independently described alterations in APP metabolism/concentration in platelets of Alzheimer patients when compared to control subjects matched for demographic characteristics. These observations defined the frame of our work aimed to investigate if a correlation between levels of platelet APP forms and Alzheimer disease could be detected. We have reported that patients affected by Alzheimer disease show a differential level of platelet APP forms. This observation has several implications: APP processing abnormalities, believed to be a very early change in Alzheimer disease in neuronal compartment, does occur in extraneuronal tissues, such as platelets, thus suggesting that Alzheimer disease is a systemic disorder; further, our data strongly indicate that a differential level of platelet APP forms can be considered a potential peripheral marker of Alzheimer disease allowing for discrimination between Alzheimer and other types of dementia with good sensitivity and specificity.

Original languageEnglish
Pages (from-to)763-770
Number of pages8
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume28
Issue number5
DOIs
Publication statusPublished - Aug 2004

Keywords

  • a disintegrin and metallo-protease, alpha-secretase
  • AD
  • ADAM
  • Alzheimer Disease
  • Alzheimer disease
  • Amyloid Precursor Protein
  • Amyloid Precursor Protein isoform ratio
  • APP
  • APPr
  • BACE
  • beta-amyloid
  • Diagnosis
  • Eziopathogenesis
  • Platelets

ASJC Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

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