title: Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice.
abstract: Alzheimer's disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-β (Aβ) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aβ aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently inhibited the formation of Aβ fibrils and Aβ oligomers in vitro. Moreover, daily TRF supplementation to AβPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aβ immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain, and eventually improved cognitive function in the novel object recognition test compared with control AβPPswe/PS1dE9 mice. The present result indicates that TRF reduced amyloid pathology and improved cognitive functions, and suggests that TRF is a potential therapeutic agent for AD.
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.|Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Nor Faeizah
authors.initials: NF
authors.lastname: Ibrahim
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Yanagisawa
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.|Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Lina Wati
authors.initials: LW
authors.lastname: Durani
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.|Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Hamizah Shahirah
authors.initials: HS
authors.lastname: Hamezah
authors.affiliation: Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Hanafi Ahmad
authors.initials: HA
authors.lastname: Damanhuri
authors.affiliation: Department of Biochemistry, Faculty of Medicine, UKMMC, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, Malaysia.
authors.forename: Wan Zurinah
authors.initials: WZ
authors.lastname: Wan Ngah
authors.affiliation: Department of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kiuchi
authors.affiliation: Department of Neurology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Tooyama
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D000682:Amyloid / Q000187:drug effects / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D024508:Tocotrienols / Q000627:therapeutic use*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D010446:Peptide Fragments; D053764:Presenilin-1; D024508:Tocotrienols; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; AβPP/PS1 mice; amyloid-β; tocotrienol-rich fraction; vitamin E