title: Arachidonic or Docosahexaenoic Acid Diet Prevents Memory Impairment in Tg2576 Mice.
abstract: 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 γ-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, Aβ(1- 42)/Aβ(1- 40) ratio decreased in 14-month-old 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 Aβ(1- 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.
authors.affiliation: Department of Chemistry and Life Science, Nihon University Graduate School of Bioresource Sciences, Fujisawa, Japan.|Department of Alzheimer's Disease, National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hosono
authors.affiliation: Division of Clinical Sciences and Neuropsychopharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.|NPO Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mouri
authors.affiliation: Department of Alzheimer's Disease, National Center for Geriatrics and Gerontology, Obu, Japan.|Department of Molecular Pathology, Institute of Biomedical Science, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Nishitsuji
authors.affiliation: Department of Alzheimer's Disease, National Center for Geriatrics and Gerontology, Obu, Japan.|Department of Neurophysiology and Brain Science, Nagoya City University, School of Medical Sciences, Nagoya, Japan.
authors.forename: Cha-Gyun
authors.initials: CG
authors.lastname: Jung
authors.affiliation: Institute for Health Care Science, Suntory Wellness Ltd., Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kontani
authors.affiliation: Institute for Health Care Science, Suntory Wellness Ltd., Osaka, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Institute for Health Care Science, Suntory Wellness Ltd., Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Institute for Health Care Science, Suntory Wellness Ltd., Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: NPO Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.|Nabeshima Laboratory, Department of Pharmacy, Meijyo University, Nagoya, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabehsima
authors.affiliation: Department of Alzheimer's Disease, National Center for Geriatrics and Gerontology, Obu, Japan.|Department of Biochemistry, Nagoya City University, School of Medical Sciences, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Michikawa
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D016718:Arachidonic Acid / Q000627:therapeutic use*; D001245:Association Learning / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003213:Conditioning, Psychological / Q000502:physiology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004622:Embryo, Mammalian; D005239:Fear / Q000523:psychology; D005260:Female; D006801:Humans; D008569:Memory Disorders / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid
keywords: Alzheimer’s disease; amyloid β-protein; amyloid β-protein precursor; arachidonic acid; docosahexaenoic acid; memory impairment