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Coenzyme Q10 Attenuates β-Amyloid Pathology in the Aged Transgenic Mice with Alzheimer Presenilin 1 Mutation

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Abstract

One of the neuropathological features of Alzheimer’s disease (AD) is the deposition of senile plaques containing β-amyloid (Aβ). There is limited evidence for the treatment to arrest Aβ pathology of AD. In our present study, we tested the effect of coenzyme Q10 (CoQ10), an endogenous antioxidant and a powerful free radical scavenger, on Aβ in the aged transgenic mice overexpressing Alzheimer presenilin 1-L235P (leucine-to-proline mutation at codon 235, 16–17 months old). The treatment by feeding the transgenic mice with CoQ10 for 60 days (1,200 mg kg−1 day−1) partially attenuated Aβ overproduction and intracellular Aβ deposit in the cortex of the transgenic mice compared with the age-matched untreated transgenic mice. Meanwhile, an increased oxidative stress reaction was detected as evidenced by elevated level of malondialdehyde (MDA) and decreased activity of superoxide dismutase (SOD) in the transgenic mice relative to the wild-type mice, and supplementation of CoQ10 partially decreased MDA level and upregulated the activity of SOD. The results indicate that oxidative stress is enhanced in the brain of the transgenic mice, that this enhancement may further promote Aβ42 overproduction in a vicious formation, and that CoQ10 would be beneficial for the therapy of AD.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

β-amyloid

CoQ10:

coenzyme Q10

PS-1:

presenilin 1

MDA:

malondialdehyde

SOD:

superoxide dismutase

References

  • Beal, M. F., & Shults, C. W. (2003). Effects of Coenzyme Q10 in Huntington’s disease and early Parkinson’s disease. Biofactors, 18(1–4), 153–161.

    PubMed  CAS  Google Scholar 

  • Behl, C., Davis, J. B., Lesley, R., & Schubert, D. (1994). Hydrogen peroxide mediates amyloid beta protein toxicity. Cell, 77(6), 817–827.

    Article  PubMed  CAS  Google Scholar 

  • Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., et al. (1996). Familial Alzheimer’s disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron, 17(5), 1005–1013.

    Article  PubMed  CAS  Google Scholar 

  • Borek, C. (2004). Anti-aging effects of CoQ10. AgroFood Industry Hi-Tech, 15, 24–27.

    CAS  Google Scholar 

  • Boyd-Kimball, D., Sultana, R., Mohmmad-Abdul, H., & Butterfield, D. A. (2004). Rodent Abeta(1-42) exhibits oxidative stress properties similar to those of human Abeta(1-42): Implications for proposed mechanisms of toxicity. Journal of Alzheimer’s Disease, 6(5), 515–525.

    PubMed  CAS  Google Scholar 

  • Butterfield, D. A., Koppal, T., Subramaniam, R., & Yatin, S. (1999). Vitamin E as an antioxidant/free radical scavenger against amyloid beta-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: Insights into Alzheimer’s disease. Reviews in the Neurosciences, 10(2), 141–149.

    PubMed  CAS  Google Scholar 

  • Cetin, F., & Dincer, S. (2007). The effect of intrahippocampal beta amyloid (1-42) peptide injection on oxidant and antioxidant status in rat brain. Annals of the New York Academy of Sciences, 1100, 510–517.

    Article  PubMed  CAS  Google Scholar 

  • Chan, A., & Shea, T. B. (2006). Supplementation with apple juice attenuates presenilin-1 overexpression during dietary and genetically-induced oxidative stress. Journal of Alzheimer’s Disease, 10(4), 353–358.

    PubMed  CAS  Google Scholar 

  • Chui, D. H., Tanahashi, H., Ozawa, K., Ikeda, S., Checler, F., Ueda, O., et al. (1999). Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Natural Medicines, 5(5), 560–564.

    Article  CAS  Google Scholar 

  • Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., et al. (1997). Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Natural Medicines, 3(1), 67–72.

    Article  CAS  Google Scholar 

  • Cole, G. M., & Frautschy, S. A. (2006). Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer’s disease mouse model. Nutrition & Health, 18(3), 249–259.

    CAS  Google Scholar 

  • Coma, M., Guix, F. X., Ill-Raga, G., Uribesalgo, I., Alameda, F., Valverde, M. A., et al. (2007). Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells. Neurobiol Aging (in press).

  • Dai, X., Sun, Y., & Jiang, Z. (2007). Protective effects of vitamin E against oxidative damage induced by Abeta1-40Cu(II) complexes. Acta Biochimica et Biophysica Sinica (Shanghai), 39(2), 123–130.

    Article  CAS  Google Scholar 

  • Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C. M., Perez-tur, J., Hutton, M., et al. (1996). Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature, 383(6602), 710–713.

    Article  PubMed  CAS  Google Scholar 

  • Durany, N., Münch, G., Michel, T., & Riederer, P. (1999). Investigations on oxidative stress and therapeutical implications in dementia. European Archives of Psychiatry and Clinical Neuroscience, 249(Suppl 3), 68–73.

    PubMed  Google Scholar 

  • Ferrante, K. L., Shefner, J., Zhang, H., Betensky, R., O’Brien, M., Yu, H., et al. (2005). Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology, 65(11), 1834–1836.

    Article  PubMed  CAS  Google Scholar 

  • Filipcik, P., Cente, M., Ferencik, M., Hulin, I., & Novak, M. (2006). The role of oxidative stress in the pathogenesis of Alzheimer’s disease. Bratislavske Lekarske Listy, 107(9–10), 384–394.

    PubMed  CAS  Google Scholar 

  • Gazdík, F., Piják, M. R., Borová, A., & Gazdíková, K. (2003). Biological properties of coenzyme Q10 and its effects on immunity. Casopis Lekaru Ceskych, 142(7), 390–393.

    PubMed  Google Scholar 

  • Golde, T. E., Eckman, C. B., & Younkin, S. G. (2000). Biochemical detection of Abeta isoforms: Implications for pathogenesis, diagnosis, and treatment of Alzheimer’s disease. Biochimica Et Biophysica Acta, 1502(1), 172–187.

    PubMed  CAS  Google Scholar 

  • Gouras, G. K., Almeida, C. G., & Takahashi, R. H. (2005). Intraneuronal Abeta accumulation and origin of plaques in Alzheimer’s disease. Neurobiology of Aging, 26(9), 1235–1244.

    Article  PubMed  CAS  Google Scholar 

  • Huang, X. G., Yee, B. K., Nag, S., Chan, S. T., & Tang, F. (2003). Behavioral and neurochemical characterization of transgenic mice carrying the human presenilin-1 gene with or without the leucine-to-proline mutation at codon 235. Experimental Neurology, 183(2), 673–681.

    Article  PubMed  CAS  Google Scholar 

  • Jang, M. H., Piaom, X. L., Kimm, H. Y., Cho, E. J., Baek, S. H., Kwon, S. W., et al. (2007). Resveratrol oligomers from Vitis amurensis attenuate beta-amyloid-induced oxidative stress in PC12 cells. Biological & Pharmaceutical Bulletin, 30(6), 1130–1134.

    Article  CAS  Google Scholar 

  • Kovacs, D. M., & Tanzi, R. E. (1998). Monogenic determinants of familial Alzheimer’s disease: Presenilin-1 mutations. Cellular and Molecular Life Sciences, 54(9), 902–909.

    Article  PubMed  CAS  Google Scholar 

  • Kowalska, A. (2004). The beta-amyloid cascade hypothesis: A sequence of events leading to neurodegeneration in Alzheimer’s disease. Neurologia I Neurochirurgia Polska, 38(5), 405–411.

    PubMed  Google Scholar 

  • Li, G., Zou, L. Y., Cao, C. M., & Yang, E. S. (2005). Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen-glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore. Biofactors, 25(1–4), 97–107.

    PubMed  Google Scholar 

  • Li, G., Zou, L., Jack, C. R., Yang, Y., & Yang, E. S. (2007). Neuroprotective effect of Coenzyme Q10 on ischemic hemisphere in aged mice with mutations in the amyloid precursor protein. Neurobiology of Aging, 28(6), 877–882.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Q., Xie, F., Rolston, R., Moreira, P. I., Nunomura, A., Zhu, X., et al. (2007). Prevention and treatment of Alzheimer disease and aging: Antioxidants. Mini Reviews in Medical Chemistry, 7(2), 171–180.

    Article  CAS  Google Scholar 

  • Markesbery, W. R. (1997). Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biology & Medicine, 23(1), 134–147.

    Article  CAS  Google Scholar 

  • Markesbery, W. R., & Carney, J. M. (1999). Oxidative alterations in Alzheimer’s disease. Brain Pathology, 9(1), 133–146.

    Article  PubMed  CAS  Google Scholar 

  • Misonou, H., Morishima-Kawashima, M., & Ihara, Y. (2000). Oxidative stress induces intracellular accumulation of amyloid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry, 39(23), 6951–6959.

    Article  PubMed  CAS  Google Scholar 

  • Ohyagi, Y., & Tabira, T. (2006). Intracellular amyloid beta-protein and its associated molecules in the pathogenesis of Alzheimer’s disease. Mini Reviews in Medical Chemistry, 6(10), 1075–1080.

    Article  CAS  Google Scholar 

  • Paola, D., Domenicotti, , , C., Nitti, M., Vitali, A., Borghi, R., Cottalasso, D., et al. (2000). Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochemical and Biophysical Research Communications, 268(2), 642–646.

    Article  PubMed  CAS  Google Scholar 

  • Qu, Z. S., Tian, Q., Zhou, X. W., Wang, X. C., Wang, Q., Zhang, Q., et al. (2005). Alteration of beta-amyloid and glutamate transporter in the brain of diabetes rats and the underlying mechanism. Zhongguo Yi Xue Ke Xue Yuan Xue Bagao, 27(6), 708–711.

    CAS  Google Scholar 

  • Schellenberg, G. D., D’Souza, I., & Poorkaj, P. (2000). The genetics of Alzheimer’s disease. Current Psychiatry Reports, 2(2), 158–164.

    Article  PubMed  CAS  Google Scholar 

  • Shults, C. W., Oakes, D., Kieburtz, K., Beal, M. F., Haas, R., Plumb, S., et al. (2002). Parkinson Study Group.Effects of coenzyme Q10 in early Parkinson disease: Evidence of slowing of the functional decline. Archives of Neurology, 59(10), 1541–1550.

    Article  PubMed  Google Scholar 

  • St George-Hyslop, P. H. (2000). Molecular genetics of Alzheimer’s disease. Biological Psychiatry, 47(3), 183–199.

    Article  PubMed  CAS  Google Scholar 

  • Sultana, R., Perluigi, M., & Butterfield, D. A. (2006). Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer’s disease: Insights into mechanism of neurodegeneration from redox proteomics. Antioxidants & Redox Signalling, 8(11–12), 2021–2037.

    Article  CAS  Google Scholar 

  • Sultana, R., Ravagna, A., Mohmmad-Abdul, H., Calabrese, V., & Butterfield, D. A. (2005). Ferulic acid ethyl ester protects neurons against amyloid beta-peptide(1-42)-induced oxidative stress and neurotoxicity: Relationship to antioxidant activity. Journal of Neurochemistry, 92(4), 749–758.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Z. F., Li, H. L., Li, X. C., Zhang, Q., Tian, Q., Wang, Q., et al. (2006). Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture. Journal of Neurochemistry, 98(4), 1167–1175.

    Article  PubMed  CAS  Google Scholar 

  • Xia, W. (2000). Role of presenilin in gamma-secretase cleavage of amyloid precursor protein. Experimental Gerontology, 35(4), 453–460.

    Article  PubMed  CAS  Google Scholar 

  • Xiong, K., Cai, H., Luo, X. G., Struble, R. G., Clough, R. W., & Yan, X. X. (2007). Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina. Experimental Brain Research, 181, 435–446.

    Article  CAS  Google Scholar 

  • Zheng, L., Roberg, K., Jerhammar, F., Marcusson, J., & Terman, A. (2006). Oxidative stress induces intralysosomal accumulation of Alzheimer amyloid beta-protein in cultured neuroblastoma cells. Annals of the New York Academy of Sciences, 1067, 248–251.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This study was supported by grants from Rejuvenis, Hong Kong Jockey Club Charities Trust, Hong Kong Research Grants Council (RGC), and the Deutscher Akademischer Austausch Dienst (German Academic Exchange Service, DAAD; RGC Project no. G HK023/06), RGC Seed Funding Programme for Basic Research 2006–2007, and the National Natural Science Foundation of China (30700277).

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Authors and Affiliations

  1. The Jockey Club MRI Center, The University of Hong Kong, Hong Kong, China

    Xifei Yang, Geng Li & Edward S Yang

  2. Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xifei Yang, Ying Yang & Jianzhi Wang

  3. Hong Kong Applied Science and Technology Research, Institute Company Limited, Hong Kong, China

    Geng Li & Edward S Yang

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  1. Xifei Yang
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  2. Ying Yang
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Correspondence to Geng Li.

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Yang, X., Yang, Y., Li, G. et al. Coenzyme Q10 Attenuates β-Amyloid Pathology in the Aged Transgenic Mice with Alzheimer Presenilin 1 Mutation. J Mol Neurosci 34, 165–171 (2008). https://doi.org/10.1007/s12031-007-9033-7

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  • DOI: https://doi.org/10.1007/s12031-007-9033-7

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