期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 24, 期 4, 页码 669-679出版社
IOS PRESS
DOI: 10.3233/JAD-2011-101512
关键词
Angiotensin I/II; angiotensinogen; cholesterol; 24-hydroxycholesterol; mild cognitive impairment; neurodegeneration
资金
- Swedish Brain Power
- Riskbankens jubileumsfond
- Gun och Bertil Stohnes Stiftelse
- Karolinska Institutet fund for geriatric research
- Stiftelsen Gamla Tjanarinnor
- Swedish Research Council
- Alzheimerfonden
In spite of the fact that cholesterol does not pass the blood-brain barrier (BBB), hypercholesterolemia has been linked to increased Alzheimer's disease (AD) risk. Hypertension is another risk factor and angiotensin converting enzyme (ACE) activity is known to be increased in AD. Furthermore, a lower incidence of AD has been reported in patients taking anti-hypertensive drugs. Here we show that the levels of angiotensinogen (AGT) and ACE are increased in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and AD. Moreover, we show ACE activity in the CSF to be positively correlated with both plasma and CSF levels of 27-hydroxycholesterol (27-OH), an oxysterol known to pass through the BBB and taken up from the circulation by the brain. In addition, treatment of rat primary neurons, astrocytes, and human neuroblastoma cells with 27-OH resulted in increased production of AGT. Our results demonstrate that upregulation of renin-angiotensin system (RAS) in AD brains occurs not only at the enzymatic level (ACE) but also at the substrate level (AGT). The possibility that 27-OH is part of a mechanism linking hypercholesterolemia with increased brain RAS activity and increased AD risk is discussed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据