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School of Biosciences John Harwood Bruce Caterson Clare Hughes

Alzheimer’s Research Network - May 23 rd 2008. How may dietary n-3 polyunsaturated fatty acids alleviate Alzheimer's disease?. School of Biosciences John Harwood Bruce Caterson Clare Hughes. Cécile Bascoul. School of Psychology Mark Good. Docosahexaenoic acid (DHA). 2. 1. 3.

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School of Biosciences John Harwood Bruce Caterson Clare Hughes

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  1. Alzheimer’s Research Network - May 23rd 2008 How may dietary n-3 polyunsaturated fatty acids alleviate Alzheimer's disease? School of Biosciences John Harwood Bruce Caterson Clare Hughes Cécile Bascoul School of Psychology Mark Good

  2. Docosahexaenoic acid (DHA) 2 1 3 • Constituent of phospholipids of the cells plasma membrane • DHA is a polyunsaturated fatty acid (22:6n-3) • In rat brain, DHA constitutes > 17% of the total fatty acids (Horrocks and Farooqui, 2004) • Source: fatty fish • DHA precursors: EPA (20:5n-3) and ALA (18:3n-3)

  3. In human: • DHA in hippocampus of AD patients. • Dietary n-3 fatty acids or fish risk of AD. • In mouse/rat models: • DHA Aβ in AD mouse model. • DHA impairment of learning and memory in Aβ-infused rats. Positive effects of DHA on AD

  4. Normal diet + 5% DHA + 5% control oil Tg Tg WT WT Methods • Experiment on mice WT and Tg2576 (APPsw) • Behavioural changes • Biochemical changes

  5. Foraging experiment • Males + females • Diets at 4 months • 12 months of age ? 1 error = 1 return

  6. ALZHEIMER’S MOUSE NORMAL MOUSE 8 min 30s 8 errors 1 min 35s 1 error

  7. Average mean errors (mean ± SEM) (n = 12) (n = 10) (n = 11) (n = 10) ANOVA: Significant progression with sessions (p = 0.003) Significant effect of genotype (p = 0.013) Non-significant effect of diet (p = 0.132)

  8. (mean ± SD) DHA is incorporated in cortex, cerebellum and hippocampus Main fatty acids: > 2% of total fatty acids

  9. Individual phospholipids - TLC Mouse brain lipids DPG PE PC PS Sph 1st PI 2nd

  10. Main fatty acids in cortex phosphatidylinositol (PI) (mean ± SD) sn-1 (16:0) sn-2 (18:0) PI head group Fatty acids over 2% of the total fatty acids

  11. Main fatty acids in cortex phosphatidylethanolamine (PE) (mean ± SD) sn-1 (18:0) sn-2 (DHA) PE head group Fatty acids over 2% of the total fatty acids

  12. Mass Spectrometry PE molecular species in cortex (mean ± SEM) * * * * * * * *

  13. Q-PCR analysis (mean ± SD) In female, significant effect of genotype(p = 0.02), diet (p = 0.02) and brain area (p = 0.01). In male, non-significant effect of genotype (p = 0.18), diet (p = 0.50) and brain area (p = 0.66).

  14. Immunohistochemistry: Aβ 1-40 Tg oil Tg oil 173 Tg oil 189 Tg oil 180 Tg DHA Tg DHA 159 Tg DHA 135 Tg DHA 149 (21 months of age)

  15. Conclusions • DHA is incorporated in the brain, mainly in PE. • Cognitive improvement with DHA rich diet may be due to a reduced inflammation.

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