title: Vitamin C restores behavioral deficits and amyloid-β oligomerization without affecting plaque formation in a mouse model of Alzheimer's disease.
abstract: Oxidative stress is related to the pathogenesis of Alzheimer's disease (AD) characterized by progressive memory impairment. Soluble amyloid-β (Aβ) oligomers cause cognitive loss and synaptic dysfunction rather than senile plaques in AD. The decline of the antioxidant status is associated with dementia in AD patients, especially low levels of vitamin C. Our group previously reported a relationship between anti-aging and supplementation of vitamin C derivatives. Here we report that vitamin C mitigated Aβ oligomer formation and behavioral decline in an AD mouse model treated with a vitamin C solution for 6 months. The attenuation of Aβ oligomerization was accompanied with a marked decrease in brain oxidative damage and in the ratio of soluble Aβ₄₂ to Aβ₄₀, a typical indicator of AD progression. Furthermore, the intake of vitamin C restored the declined synaptophysin and the phosphorylation of tau at Ser396. On the other hand, brain plaque deposition was not altered by the dietary intake of vitamin C. These results support that vitamin C is a useful functional nutrient for the prevention of AD.
authors.affiliation: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Murakami
authors.forename: Nakaba
authors.initials: N
authors.lastname: Murata
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kinoshita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000544:Alzheimer Disease / Q000150:complications; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D001523:Mental Disorders / Q000178:diet therapy* / Q000209:etiology; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000209:etiology; D050050:Protein Carbonylation / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; D016708:Synaptophysin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D005978:Glutathione; D001205:Ascorbic Acid