期刊
JOURNAL OF NEUROCHEMISTRY
卷 144, 期 1, 页码 81-92出版社
WILEY
DOI: 10.1111/jnc.14249
关键词
Alzheimer's disease; blood-brain barrier; cognitive function; docosahexaenoic acid; fatty acid-binding protein; omega-3 fatty acids
资金
- Judith Jane Mason and Harold Stannett Williams Memorial Foundation
- William Buckland Foundation
Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.112.6% decrease in the BBB transport of C-14-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1E9) relative to wild-type mice, associated with a 34.5 +/- 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 +/- 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.
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