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Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.
Brain. 2010 May; 133(Pt 5):1342-51.B

Abstract

Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.

Authors+Show Affiliations

Department of Neurology, Zhongshan Hospital & Shanghai Medical College, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20385653

Citation

Pan, Xiaoli, et al. "Powerful Beneficial Effects of Benfotiamine On Cognitive Impairment and Beta-amyloid Deposition in Amyloid Precursor Protein/presenilin-1 Transgenic Mice." Brain : a Journal of Neurology, vol. 133, no. Pt 5, 2010, pp. 1342-51.
Pan X, Gong N, Zhao J, et al. Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain. 2010;133(Pt 5):1342-51.
Pan, X., Gong, N., Zhao, J., Yu, Z., Gu, F., Chen, J., Sun, X., Zhao, L., Yu, M., Xu, Z., Dong, W., Qin, Y., Fei, G., Zhong, C., & Xu, T. L. (2010). Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain : a Journal of Neurology, 133(Pt 5), 1342-51. https://doi.org/10.1093/brain/awq069
Pan X, et al. Powerful Beneficial Effects of Benfotiamine On Cognitive Impairment and Beta-amyloid Deposition in Amyloid Precursor Protein/presenilin-1 Transgenic Mice. Brain. 2010;133(Pt 5):1342-51. PubMed PMID: 20385653.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. AU - Pan,Xiaoli, AU - Gong,Neng, AU - Zhao,Jing, AU - Yu,Zhe, AU - Gu,Fenghua, AU - Chen,Jia, AU - Sun,Xiaojing, AU - Zhao,Lei, AU - Yu,Meijing, AU - Xu,Zhiru, AU - Dong,Wenxin, AU - Qin,Yan, AU - Fei,Guoqiang, AU - Zhong,Chunjiu, AU - Xu,Tian-Le, Y1 - 2010/04/12/ PY - 2010/4/14/entrez PY - 2010/4/14/pubmed PY - 2010/5/18/medline SP - 1342 EP - 51 JF - Brain : a journal of neurology JO - Brain VL - 133 IS - Pt 5 N2 - Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/20385653/Powerful_beneficial_effects_of_benfotiamine_on_cognitive_impairment_and_beta_amyloid_deposition_in_amyloid_precursor_protein/presenilin_1_transgenic_mice_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awq069 DB - PRIME DP - Unbound Medicine ER -