| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-11-30 |
| タイトル |
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タイトル |
Endothelial expression of human amyloid precursor protein leads to amyloid β in the blood and induces cerebral amyloid angiopathy in knock-in mice |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Yuriko Tachida
Saori Miura
Yui Muto
Takuwa Hiroyuki
Naruhiko Sahara
Akihiro Shindo
Yukio Matsuba
Takashi Saito
Naoyuki Taniguchi
Yasushi Kawaguchi
Hidekazu Tomimoto
Takaomi Saido
Shinobu Kitazume
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
The deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in most patients with Alzheimer’s disease (AD). Compared with the pathology of CAA in humans, the pathology in most mouse models of AD is not as evident, making it difficult to examine the contribution of CAA to the pathogenesis of AD. On the basis of biochemical analyses that showed blood levels of soluble amyloid precursor protein (APP) in rats and mice were markedly lower than those measured in human samples, we hypothesized that endothelial APP expression would be markedly lower in rodents and subsequently generated mice that specifically express human WT APP (APP770) in endothelial cells (ECs). The resulting EC-APP770+ mice exhibited increased levels of serum Aβ and soluble APP, indicating that endothelial APP makes a critical contribution to blood Aβ levels. Even though aged EC-APP770+ mice did not exhibit Aβ deposition in the cortical blood vessels, crossing these animals with APP knock-in mice (AppNL-F/NL-F) led to an expanded CAA pathology, as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results highlight an overlooked interplay between neuronal and endothelial APP in brain vascular Aβ deposition. We propose that these EC-APP770+:AppNL-F/NL-F mice may be useful to study the basic molecular mechanisms behind the possible breakdown of the blood?brain barrier upon administration of anti-Aβ antibodies. |
| 書誌情報 |
Journal Impact IF of Journal of Biological Chemistry
巻 298,
号 6,
p. 101880,
発行日 2022-03
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| 出版者 |
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出版者 |
American Society for Biochemistry and Molecular Biology. |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0021-9258 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
35367207 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1016/j.jbc.2022.101880 |
