BACKGROUND: Separate monitoring of the cleavage products of different amyloid β precursor protein (APP) variants may provide useful information. RESULTS: We found that soluble APP770 (sAPP770) is released from inflamed endothelial cells and activated platelets as judged by ELISA. CONCLUSION: sAPP770 is an indicator for endothelial and platelet dysfunctions. SIGNIFICANCE: How sAPP770 is released in vivo has been shown. Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product, sAPP, is considered to be a possible marker for AD diagnosis, sAPP has been widely measured as a mixture of these variants. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable discrimination between endothelial and neurological dysfunctions. Using our newly developed ELISA system for sAPP770, we observed that inflammatory cytokines significantly enhanced sAPP770 secretion by endothelial cells. Furthermore, we unexpectedly found that sAPP770 was rapidly released from activated platelets. We also found that cerebrospinal fluid mainly contained sAPP695, while serum mostly contained sAPP770. Finally, to test our hypothesis that sAPP770 could be an indicator for endothelial dysfunction, we applied our APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial injury and platelet activation lead to fibrous plaque disruption and thrombus formation. Development of a biomarker is essential to facilitate ACS diagnosis in clinical practice. The results revealed that ACS patients had significantly higher plasma sAPP770 levels. Furthermore, in myocardial infarction model rats, an increase in plasma sAPP preceded the release of cardiac enzymes, currently used markers for acute myocardial infarction. These findings raise the possibility that sAPP770 can be a useful biomarker for ACS.
BACKGROUND: Separate monitoring of the cleavage products of different amyloid β precursor protein (APP) variants may provide useful information. RESULTS: We found that soluble APP770 (sAPP770) is released from inflamed endothelial cells and activated platelets as judged by ELISA. CONCLUSION:sAPP770 is an indicator for endothelial and platelet dysfunctions. SIGNIFICANCE: How sAPP770 is released in vivo has been shown. Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product, sAPP, is considered to be a possible marker for AD diagnosis, sAPP has been widely measured as a mixture of these variants. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable discrimination between endothelial and neurological dysfunctions. Using our newly developed ELISA system for sAPP770, we observed that inflammatory cytokines significantly enhanced sAPP770 secretion by endothelial cells. Furthermore, we unexpectedly found that sAPP770 was rapidly released from activated platelets. We also found that cerebrospinal fluid mainly contained sAPP695, while serum mostly contained sAPP770. Finally, to test our hypothesis that sAPP770 could be an indicator for endothelial dysfunction, we applied our APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial injury and platelet activation lead to fibrous plaque disruption and thrombus formation. Development of a biomarker is essential to facilitate ACS diagnosis in clinical practice. The results revealed that ACS patients had significantly higher plasma sAPP770 levels. Furthermore, in myocardial infarction model rats, an increase in plasma sAPP preceded the release of cardiac enzymes, currently used markers for acute myocardial infarction. These findings raise the possibility that sAPP770 can be a useful biomarker for ACS.
Authors: Sarah E Vermeer; Niels D Prins; Tom den Heijer; Albert Hofman; Peter J Koudstaal; Monique M B Breteler Journal: N Engl J Med Date: 2003-03-27 Impact factor: 91.245
Authors: James A R Nicoll; David Wilkinson; Clive Holmes; Phil Steart; Hannah Markham; Roy O Weller Journal: Nat Med Date: 2003-03-17 Impact factor: 53.440
Authors: J E Adams; G A Sicard; B T Allen; K H Bridwell; L G Lenke; V G Dávila-Román; G S Bodor; J H Ladenson; A S Jaffe Journal: N Engl J Med Date: 1994-03-10 Impact factor: 91.245
Authors: Annika Olsson; Kina Höglund; Magnus Sjögren; Niels Andreasen; Lennart Minthon; Lars Lannfelt; Katharina Buerger; Hans Jürgen Möller; Harald Hampel; Pia Davidsson; Kaj Blennow Journal: Exp Neurol Date: 2003-09 Impact factor: 5.330
Authors: Stephanie A Planque; Yasuhiro Nishiyama; Sari Sonoda; Yan Lin; Hiroaki Taguchi; Mariko Hara; Steven Kolodziej; Yukie Mitsuda; Veronica Gonzalez; Hameetha B R Sait; Ken-ichiro Fukuchi; Richard J Massey; Robert P Friedland; Brian O'Nuallain; Einar M Sigurdsson; Sudhir Paul Journal: J Biol Chem Date: 2015-02-27 Impact factor: 5.157