Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels

J Neurosci. 2007 Apr 18;27(16):4385-95. doi: 10.1523/JNEUROSCI.0055-07.2007.

Abstract

The underlying cause of sporadic Alzheimer disease (AD) is unknown, but a number of environmental and genetic factors are likely to be involved. One environmental factor that is increasingly being recognized as contributing to brain aging is diet, which has evolved markedly over modern history. Here we show that dietary supplementation with docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, in the 3xTg-AD mouse model of AD reduced the intraneuronal accumulation of both amyloid-beta (Abeta) and tau. In contrast, combining DHA with n-6 fatty acids, either arachidonic acid or docosapentaenoic acid (DPAn-6), diminished the efficacy of DHA over a 12 month period. Here we report the novel finding that the mechanism accounting for the reduction in soluble Abeta was attributable to a decrease in steady-state levels of presenilin 1, and not to altered processing of the amyloid precursor protein by either the alpha- or beta-secretase. Furthermore, the presence of DPAn-6 in the diet reduced levels of early-stage phospho-tau epitopes, which correlated with a reduction in phosphorylated c-Jun N-terminal kinase, a putative tau kinase. Collectively, these results suggest that DHA and DPAn-6 supplementations could be a beneficial natural therapy for AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / biosynthesis
  • Animals
  • Brain Chemistry
  • Cells, Cultured
  • Cyclin-Dependent Kinase 5
  • Dietary Supplements
  • Docosahexaenoic Acids / administration & dosage*
  • Fatty Acids / analysis
  • Fatty Acids, Unsaturated / administration & dosage*
  • Glycogen Synthase Kinase 3
  • Mice
  • Mice, Transgenic
  • Presenilin-1 / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • tau Proteins / analysis
  • tau Proteins / biosynthesis

Substances

  • Amyloid beta-Peptides
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Presenilin-1
  • tau Proteins
  • Docosahexaenoic Acids
  • Cyclin-Dependent Kinase 5
  • Protein-Serine-Threonine Kinases
  • tau protein kinase II
  • Glycogen Synthase Kinase 3
  • tau-protein kinase
  • docosapentaenoic acid