Arachidonic or docosahexaenoic acid diet prevents memory impairment in Tg2576 mice

Takashi Hosono, Akihiro Mouri, Kazuchika Nishitsuji, Cha Gyun Jung, Masanori Kontani, Hisanori Tokuda, Hiroshi Kawashima, Hiroshi Shibata, Toshiharu Suzuki, Toshitaka Nabehsima, Makoto Michikawa

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


It is believed that the amyloid β-protein (Aβ) plays a causative role in the development of Alzheimer's disease (AD). The amyloid-β protein precursor (AβPP), a substrate of Aβ, and β-secretase and β-secretase complex proteins, which process AβPP to generate Aβ, are all membrane proteins. Thus, it is reasonable to assume that alterations in brain lipid metabolism modulate AβPP and/or Aβ metabolism. However, the role of cellular polyunsaturated fatty acids in AβPP processing has not been completely understood yet.We report here that 4 months of treatment of Tg2576 mice with an arachidonic acid (ARA)-or a docosahexaenoic acid (DHA)-containing (ARA+ or DHA+) diet prevented memory impairment at 13 months of age. Although, AβPP processing to generate soluble AβPP and induce Aβ synthesis was enhanced, Aβ1-42/Aβ1-40 ratio decreased in 14-monthold Tg2576 mice fed with the ARA+ or DHA+ diet. The ARA+ or DHA+ diet did not alter the AβPP levels and the expression levels of Aβ-degrading enzymes. In cortical primary neuron cultures, ARA or DHA treatment also increased soluble AβPP and Aβ1-40 levels, and decreased Aβ 1-42/Aβ 1-40 ratio, which are similar to what were observed in Tg2576 mice fed with ARA+ or DHA+ diet. These findings suggest that not only the DHA+ diet, but also the ARA+ diet could prevent cognitive dysfunction in Tg2576 mice through the alteration of AβPP processing.

Original languageEnglish
Pages (from-to)149-162
Number of pages14
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 28-08-2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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