Endothelial APP expression exacerbates cerebral amyloid angiopathy in AD model mice Development of new models and analysis methods/amyloid/Abeta

• Published in: Alzheimer's & dementia Vol. 16; no. S2
• Main Authors: Tachida, Yuriko, Ogasawara, Naomi, Saito, Takashi, Shindo, Akihiro, Kawaguchi, Yasushi, Tomimoto, Hidekazu, Saido, Takaomi C., Kitazume, Shinobu
• Format: Journal Article
• Language: English
• Published: 01-12-2020
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.042234

Abstract
Background
Most AD patients show accumulation of Ab peptides in both brain parenchyma and blood vessels. We recently found that brain vascular endothelial cells specifically express APP770 and produces Ab40/42. We then expect endothelial APP770 could contribute to cerebral amyloid angiopathy (CAA).
Method
We first generated conditional transgenic mice harboring loxP‐neo(R)‐loxP‐APP770
NL
, (APP770(flox)), then crossed with the mice with Tie2‐Cre mice that specifically express Cre recombinase in their endothelial cells. We then crossed the mice with AD model mice,
App
NL‐F
.
Result
We found that aged endothelial APP770
NL
expressing mice exhibit Ab deposition in brain vessels but not the parenchyma. Remarkably, not all but some of the aged transgenic mice show cerebral hemorrhage. By crossing this CAA model mice with AD model mice, massive CAA pathology was observed.
Conclusion
These findings highlight the contribution of endothelial APP770 to vascular Ab deposition.