title: Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.
abstract: Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer's disease and to identify the responsible component. Here, in a mouse model of Alzheimer's disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer's disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.
authors.affiliation: Central Laboratories for Key Technologies, Kirin Company Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0004, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Ano
authors.affiliation: Graduate School of Agricultural and Life Sciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Central Laboratories for Key Technologies, Kirin Company Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0004, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Kutsukake
authors.affiliation: Koiwai Dairy Products Co., Ltd., 36-1 Maruyachi, Shizukuishi-cho, Iwate, 020-0507, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sugiyama
authors.affiliation: Graduate School of Agricultural and Life Sciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Central Laboratories for Key Technologies, Kirin Company Ltd., 1-13-5 Fukuura Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0004, Japan.
authors.forename: Aruto
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Graduate School of Agricultural and Life Sciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakayama
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D043302:Cultured Milk Products / Q000737:chemistry* / Q000382:microbiology; D005260:Female; D005285:Fermentation; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009829:Oleic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D010407:Penicillium / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D009829:Oleic Acids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C029407:oleylamide