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 language | English (US) |
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Pages (from-to) | 53-58 |
Number of pages | 6 |
Journal | Journal of the Neurological Sciences |
Volume | 240 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 15 2006 |
Keywords
- APP
- Alzheimer's disease
- Platelets
- α-Secretase
- β-Amyloid
- β-Secretase
ASJC Scopus subject areas
- Neurology
- Clinical Neurology