Impact of DHA and EPA Supplementation on Alzheimer's-Like Symptoms in Mice
This chat discusses a study on how n-3 PUFAs, particularly DHA and EPA, affect cognitive performance and Alzheimer’s pathology in mice. Findings highlight increased DHA in the brain, decreased phosphorylated tau, and specific benefits of high EPA intake, though no change in amyloid-beta levels was observed.
tldr for : Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) improves cognitive performance in several animal models of Alzheimer's disease (AD), an effect often associated with reduced amyloid-beta (Aβ) and/or tau pathologies. However, it remains unclear to what extent eicosapentaenoic (EPA) provides additional benefits compared to docosahexaenoic acid (DHA). Here, male and female 3xTg-AD mice were fed for 3 months (13 to 16 months of age) the following diets: (1) control (no DHA/EPA), (2) DHA (1.1g/kg) and low EPA (0.4g/kg), or (3) DHA (0.9g/kg) with high EPA (9.2g/kg). The DHA and DHA+EPA diets respectively increased DHA by 19% and 8% in the frontal cortex of 3xTg-AD mice, compared to controls. Levels of EPA, which were below the detection limit after the control diet, reached 0.14% and 0.29% of total brain fatty acids after the DHA and DHA+EPA diet, respectively. DHA and DHA+EPA diets lowered brain arachidonic acid (ARA) levels and the n-6
docosapentaenoic acid (DPA) ratio. Brain uptake of free 14C-DHA measured through intracarotid brain perfusion, but not of 14C-EPA, was lower in 3xTg-AD compared to NonTg mice. DHA and DHA+EPA diets in 3xTg-AD mice reduced cortical soluble phosphorylated tau (pS202) (-34% high-DHA, -34% DHA+EPA, p<0.05) while increasing p21 activated kinase (+58% and +83%, p<0.001; respectively). High EPA intake lowered insoluble phosphorylated tau (-31% versus DHA, p<0.05). No diet effect on Aβ levels was observed. In conclusion, dietary intake of DHA and EPA leads to differential changes in brain PUFA while altering cerebral biomarkers consistent with beneficial effects against AD-like neuropathology.?The study investigates the effects of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on cognitive performance and Alzheimer's disease-like symptoms in 3xTg-AD mice. The diets tested included control (no DHA/EPA), low DHA with low EPA, and low DHA with high EPA. Key findings include:
- DHA and DHA+EPA diets increased DHA levels in the frontal cortex by 19% and 8%, respectively, compared to controls.
- EPA levels, initially undetectable, increased with the diets containing DHA and DHA+EPA.
- Both DHA and DHA+EPA diets reduced brain arachidonic acid (ARA) levels and the n-6 docosapentaenoic acid (DPA) ratio.
- Brain uptake of DHA was lower in Alzheimer's model mice than in non-transgenic mice, while EPA uptake was not affected.
- The diets decreased levels of soluble phosphorylated tau and increased p21 activated kinase, which are biomarkers associated with Alzheimer's pathology.
- High EPA intake specifically reduced levels of insoluble phosphorylated tau.
- No significant effect on amyloid-beta (Aβ) levels was observed with the dietary interventions.
Overall, the study concludes that dietary DHA and EPA result in beneficial alterations in brain fatty acid composition and biomarkers related to Alzheimer’s disease, with high EPA intake showing additional specific benefits on phosphorylated tau pathology.
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