Platelet amyloid precursor protein processing: a bio-marker for Alzheimer's disease.
The amyloid precursor protein (APP) in brain is processed either by an amyloidogenic pathway by beta-secretase and gamma-secretase to yield Abeta (beta-amyloid 4 kDa) peptide or by alpha-secretase within the beta-amyloid domain to yield non-amyloidogenic products. We have studied blood platelet levels of a 22-kDa fragment containing the Abeta (beta-amyloid 4 kDa) peptide, beta-secretase (BACE1), alpha-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 Abeta4, increased activation of beta-secretase (BACE1), decreased activation of alpha-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.
Tang
Kun
K
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, United States.
Hynan
Linda S
LS
Baskin
Fred
F
Rosenberg
Roger N
RN
D051722:ADAM Proteins / Q000097:blood; D000072197:ADAM10 Protein; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D016282:Aspartic Acid Endopeptidases; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D010450:Endopeptidases / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008970:Molecular Weight; D010446:Peptide Fragments / Q000097:blood
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D008565:Membrane Proteins; D010446:Peptide Fragments; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human