Short-term docosahexaenoic acid rich diet prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice
Abstract
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.
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BibTeX
@article{raffoul2026shortterm,
title = {{Short-term docosahexaenoic acid rich diet prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice}},
author = {Rana Raffoul and Jessica Avila Lopez and Annick Vachon and Benoit Laurent and Mélanie Plourde},
journal = {Prostaglandins, Leukotrienes and Essential Fatty Acids},
year = {2026},
month = oct,
doi = {10.1016/j.plefa.2026.102730},
url = {https://hal.science/hal-05790348v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Short-term docosahexaenoic acid rich diet prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice
AU - Rana Raffoul
AU - Jessica Avila Lopez
AU - Annick Vachon
AU - Benoit Laurent
AU - Mélanie Plourde
PY - 2026
DA - 2026/10/09
JO - Prostaglandins, Leukotrienes and Essential Fatty Acids
DO - 10.1016/j.plefa.2026.102730
UR - https://hal.science/hal-05790348v1
AB - 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.
SN - 0952-3278
ER -