期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 51, 页码 40097-40103出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.144626
关键词
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资金
- Systems Glycobiology research project
- Ministry of Education, Science, Sports, and Culture of Japan [21570154]
- Grants-in-Aid for Scientific Research [21570154] Funding Source: KAKEN
Deposition of amyloid beta(A beta) in the brain is closely associated with Alzheimer disease (AD). A beta is generated from amyloid precursor protein (APP) by the actions of beta- and gamma-secretases. In addition to A beta deposition in the brain parenchyma, deposition of A beta in cerebral vessel walls, termed cerebral amyloid angiopathy, is observed in more than 80% of AD individuals. The mechanism for how A beta accumulates in blood vessels remains largely unknown. In the present study, we show that brain endothelial cells expressed APP770, a differently spliced APP mRNA isoform from neuronal APP695, and produced A beta 40 and A beta 42. Furthermore, we found that the endothelial APP770 had sialylated core 1 type O-glycans. Interestingly, O-glycosylated APP770 was preferentially processed by both alpha- and beta-cleavage and secreted into the media, suggesting that O-glycosylation and APP processing involved related pathways. By immunostaining human brain sections with an anti-APP770 antibody, we found that APP770 was expressed in vascular endothelial cells. Because we were able to detect O-glycosylated sAPP770 beta in human cerebrospinal fluid, this unique soluble APP770 beta has the potential to serve as a marker for cortical dementias such as AD and vascular dementia.
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