We found that soluble APP770 (sAPP770) is released from inflamed endothelial cells and activated platelets as judged by ELISA.
CONCLUSION: 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.