Reduced blood‐brain barrier expression of fatty acid‐binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega‐3 fatty acid diets
1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia;2. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia;3. Australian Centre for Research on Separation Science, School of Chemistry, Monash University, Australia;4. Department of Physiology, Biomedicine Discovery Institute, Monash University, Clayton, Vic., Australia;5. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia;6. ARC Centre of Excellence in Convergent Bio‐Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia
Abstract:
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 42.1 ± 12.6% decrease in the BBB transport of 14C‐DHA in 8‐month‐old AD transgenic mice (APPswe,PSEN1?E9) 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.
