Vitamin C Restores Behavioral Deficits and Amyloid-β Oligomerization without Affecting Plaque Formation in a Mouse Model of Alzheimer's Disease

Article type: Research Article

Authors: Murakami, Kazuma^{a; b; 1} | Murata, Nakaba^{a; c} | Ozawa, Yusuke^a | Kinoshita, Noriaki^d | Irie, Kazuhiro^b | Shirasawa, Takuji^e | Shimizu, Takahiko^{a; c; *}

Affiliations: [a] Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan | [b] Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan | [c] Applied Biological Chemistry, United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan | [d] Immuno-Biological Laboratories Co, Ltd., Gunma, Japan | [e] Department of Aging Control Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan

Correspondence: [*] Correspondence to: Takahiko Shimizu, Ph.D., Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. Tel.: +81 3 3964 3241; Fax: +81 3 3579 4776; E-mail: shimizut@tmig.or.jp.

Note: [1] Research Fellow of the Japan Society for the Promotion of Science.

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.

Keywords: Alzheimer's disease, amyloid-β, anxiety, hyperactivity, oligomer, vitamin C

DOI: 10.3233/JAD-2011-101971

Journal: Journal of Alzheimer's Disease, vol. 26, no. 1, pp. 7-18, 2011