LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human .

Compared with , is associated with greater age-related cognitive decline and higher risk of neurodegenerative disorders. Therefore, development of supplements that target genotype-modulated processes could provide a great benefit for the aging population. Evidence suggests a link between genotype and docosahexaenoic acid (DHA); however, clinical studies with current DHA supplements have produced negative results in dementia. The lack of beneficial effects with current DHA supplements may be related to limited bioavailability, as the optimal form of DHA for brain uptake is lysophosphatidylcholine (LPC)-DHA. We previously developed a method to enrich the LPC-DHA content of krill oil through lipase treatment (LT-krill oil), which resulted in fivefold higher enrichment in brain DHA levels in wild-type mice compared with untreated krill oil. Here, we evaluated the effect of a control diet, diet containing krill oil, or a diet containing LT-krill oil in - and targeted replacement mice (-TR mice; treated from 4 to 12 months of age). We found that DHA levels in the plasma and hippocampus are lower in -TR mice and that LT-krill oil increased DHA levels in the plasma and hippocampus of both - and -TR mice. In -TR mice, LT-krill oil treatment resulted in higher levels of the synaptic vesicle protein SV2A and improved performance on the novel object recognition test. In conclusion, our data demonstrate that LPC-DHA/EPA-enriched krill oil can increase brain DHA and improve memory-relevant behavior in mice that express . Therefore, long-term use of LT-krill oil supplements may on some level protect against age-related neurodegeneration.