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The effect of dietary omega-3 polyunsaturated fatty acids and curcumin on cognition and pathology in a mouse model of amyloid pathology

Hall, Katie May 2011. The effect of dietary omega-3 polyunsaturated fatty acids and curcumin on cognition and pathology in a mouse model of amyloid pathology. PhD Thesis, Cardiff University.
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Previous studies have shown that dietary supplementation of curcumin or omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid can reduce behavioural deficits and β-amyloid (Aβ) pathology in several models of Alzheimer’s disease (AD), including Tg2576 mice. However, no study to date had examined the effect of omega-3 PUFA and curcumin co-supplementation on behaviour or β-amyloid pathology in mouse models of AD. Further to this, no study to date had examined the effect of longitudinal omega-3 PUFA or curcumin supplementation provided from an early age before significant pathological development in the Tg2576 model. This was deemed important since human studies have suggested that lifelong dietary choices before disease development are an important factor in disease risk. Finally, although a plethora of studies has examined the effect of omega-3 PUFA supplementation, none has accurately examined its effect against an appropriate control diet. For example, some control diets contained differential levels of fatty acids such as excess total fat and omega-6 PUFAs. Such differences in the control diet may have contributed to the observed beneficial effects of dietary omega-3 PUFA supplementation, particularly since these dietary factors can exacerbate pathological processes related to AD. Using this experimental design, chapter 3 found longitudinal dietary supplementation of omega-3 PUFA docosahexaenoic acid (DHA) from an early age in Tg2576 mice provided some protection from cognitive decline that was limited to later but not early stages of pathology. In contrast to previous reports however, Aβ pathology was unaltered by DHA supplementation. Providing DHA supplementation from an even earlier age, chapter 4 showed that DHA reduced behavioural deficits at an early age (prior to Aβ pathology), although interestingly, these effects were less robust at the later age. Chapter 5 examined longitudinal supplementation of curcumin, fish oil containing omega-3 PUFAs (DHA and eicosapentaenoic acid, EPA) and their co-supplementation from an early age in Tg2576 mice. The results consistently revealed no beneficial effects of dietary supplementation on behaviour or Aβ pathological measures. The findings from this thesis indicate that dietary supplementation of DHA relative to a suitable control diet can provide only limited protection against behavioural deficits in Tg2576 mice. In contrast, fish oil supplementation containing omega-3 PUFAs DHA and EPA provided no protection, indicating that DHA monotherapy may be a more advisable treatment. The null effects of curcumin supplementation at earlier stages relative to previous studies suggest that curcumin may only be effective during advanced stages of pathology, although further investigation is needed. Finally, the null effects of curcumin and fish oil/omega-3 PUFA co-supplementation suggest that this is not an optimal intervention strategy in reducing Aβ-induced changes.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Funders: BBSRC
Date of First Compliant Deposit: 30 March 2016
Last Modified: 16 Apr 2019 14:42

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