Short-term docosahexaenoic acid rich diet prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice.

BACKGROUND

Metabolism of docosahexaenoic acid (DHA), an omega-3 (Ω3) fatty acid (FA), differs between carriers of the epsilon 4 allele of the apolipoprotein E (APOE4)-the main genetic risk factor for late-onset Alzheimer's disease-and APOE3 carriers. Dietary DHA has been shown to prevent cognitive decline in APOE4 carriers. However, whether DHA must be consumed the whole life is unclear. We hypothesized that a DHA intake started later in life and for a shorter duration prevents cognitive decline in APOE4 mice.

OBJECTIVE

To investigate three dietary durations of DHA on the prevention of cognitive decline in APOE4 mice.

METHODS

Mice knock-in for the human APOE3 (control, n = 84; 34 males/50 females) or APOE4 (n = 84; 39 males/45 females) allele were fed either a DHA-free control diet for 8 months or a diet rich in calcium salt DHA (0.5 g DHA/100 g diet) for 2, 4 or 8 months. Recognition memory was assessed using the novel object recognition test. DHA was quantified using gas chromatography.

RESULTS

APOE4 mice fed the control diet did not recognize the novel object as the APOE3 mice did suggesting cognitive decline in APOE4 mice. However, a DHA-Ca rich diet for 2 and 4 months prevented cognitive deficits in males (2M-P = 0.0414, 4M-P = 0.0073) and females (2M-P < 0.0001). 2-months DHA-Ca rich diet was associated with 18-25% higher cortical relative percentage of DHA in females and males compared to the control diet (Females-P = 0.0031; Males-P = 0.0010).

CONCLUSION

In APOE4 mice, it is not necessary to consume DHA-calcium salt throughout life to prevent cognitive decline.