PT  - JOURNAL ARTICLE
AU  - Yuriko Tachida
AU  - Saori Miura
AU  - Rie Imamaki
AU  - Naomi Ogasawara
AU  - Hiroyuki Takuwa
AU  - Naruhiko Sahara
AU  - Akihiro Shindo
AU  - Yukio Matsuba
AU  - Takashi Saito
AU  - Naoyuki Taniguchi
AU  - Yasushi Kawaguchi
AU  - Hidekazu Tomimoto
AU  - Takaomi Saido
AU  - Shinobu Kitazume
TI  - Endothelial expression of human APP leads to cerebral amyloid angiopathy in mice
AID  - 10.1101/2020.07.22.215418
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.22.215418
4099  - http://biorxiv.org/content/early/2020/07/22/2020.07.22.215418.short
4100  - http://biorxiv.org/content/early/2020/07/22/2020.07.22.215418.full
AB  - The deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in more than 90% of Alzheimer’s disease (AD) patients. The presence of such CAA pathology is not as evident, however, in most mouse models of AD, thereby making it difficult to examine the contribution of CAA to the pathogenesis of AD. Since blood levels of soluble amyloid precursor protein (sAPP) in rodents are less than 1% of those in humans, we hypothesized that endothelial APP expression would be markedly lower in rodents, thus providing a reason for the poorly expressed CAA pathology. Here we generated mice that specifically express human APP770 in endothelial cells. These mice exhibited an age-dependent robust deposition of Aβ in brain blood vessels but not in the parenchyma. Crossing these animals with APP knock-in mice led to an expanded CAA pathology as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results show that both neuronal and endothelial APP contribute cooperatively to vascular Aβ deposition, and suggest that this mouse model will be useful for studying disease mechanisms underlying CAA and for developing novel AD therapeutics.Competing Interest StatementThe authors have declared no competing interest.