Platelet amyloid precursor protein processing: A bio-marker for Alzheimer's disease

Kun Tang, Linda S. Hynan, Fred Baskin, Roger N. Rosenberg

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

The amyloid precursor protein (APP) in brain is processed either by an amyloidogenic pathway by β-secretase and γ-secretase to yield Aβ (β-amyloid 4 kDa) peptide or by α-secretase within the β-amyloid domain to yield non-amyloidogenic products. We have studied blood platelet levels of a 22-kDa fragment containing the Aβ (β-amyloid 4 kDa) peptide, β-secretase (BACE1), α-secretase (ADAM10), and APP isoform ratios of the 120-130 kDa to 110 kDa peptides from 31 Alzheimer's disease (AD) patients and 10 age-matched healthy control subjects. We found increased levels of Aβ4, increased activation of β-secretase (BACE1), decreased activation of α-secretase (ADAM10) and decreased APP ratios in AD patients compared to normal control subjects. These observations indicate that the blood platelet APP is processed by the same amyloidogenic and non-amyloidogenic pathways as utilized in brain and that APP processing in AD patients is altered compared to control subjects and may be a useful bio-marker for the diagnosis of AD, the progression of disease and for monitoring drug responses in clinical trials.

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalJournal of the Neurological Sciences
Volume240
Issue number1-2
DOIs
StatePublished - Jan 15 2006

Keywords

  • APP
  • Alzheimer's disease
  • Platelets
  • α-Secretase
  • β-Amyloid
  • β-Secretase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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