Endothelial APP expression exacerbates cerebral amyloid angiopathy in AD model mice: Development of new models and analysis methods/amyloid/Abeta. (7th December 2020)

• Record Type: Journal Article
• Authors: Tachida, Yuriko; Ogasawara, Naomi; Saito, Takashi; Shindo, Akihiro; Kawaguchi, Yasushi; Tomimoto, Hidekazu; Saido, Takaomi C.; Kitazume, Shinobu
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 2
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.042234
• Languages: English
• ISSNs: 1552-5260

Abstract

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.