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Peripherally Applied Synthetic Peptide isoAsp7-Aβ(1-42) Triggers Cerebral β-Amyloidosis

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Abstract

Intracerebral and intraperitoneal inoculation with β-amyloid-rich brain extracts originating from patients with Alzheimer’s disease as well as intracerebral injection of aggregates composed of synthetic Aβ can induce cerebral β-amyloidosis, and associated cognitive dysfunctions in susceptible animal hosts. We have found that repetitive intravenous administration of 100 μg of synthetic peptide corresponding to isoAsp7-containing Aβ(1-42), an abundant age-dependent Aβ isoform present both in the pathological brain and in synthetic Aβ preparations, robustly accelerates formation of classic dense-core congophilic amyloid plaques in the brain of β-amyloid precursor protein transgenic mice. Our findings indicate this peptide as an inductive agent of cerebral β-amyloidosis in vivo.

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Acknowledgments

The authors thank Dr. Alexei Adzhubei for helpful comments. This study was supported by the Molecular and Cellular Biology Program of the Russian Academy of Sciences, the Russian Foundation for Basic Research (grant 11-04-01367-a), and the Russian Federal Program (contract 11.519.11.2008). Part of this study was performed at the EIMB RAS “Genome” center, and was supported by the Russian Ministry of Education and Science, State Contract No. 16.552.11.7069.

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, 119991, Moscow, Russia

    S. A. Kozin, I. B. Cheglakov, P. O. Tsvetkov & A. A. Makarov

  2. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya Street 10, 119832, Moscow, Russia

    S. A. Kozin & A. V. Lisitsa

  3. Branch of Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Science Avenue 6, 142290, Pushchino, Moscow Region, Russia

    A. A. Ovsepyan & G. B. Telegin

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  1. S. A. Kozin
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  2. I. B. Cheglakov
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  3. A. A. Ovsepyan
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  4. G. B. Telegin
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  5. P. O. Tsvetkov
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  6. A. V. Lisitsa
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  7. A. A. Makarov
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Correspondence to S. A. Kozin or A. A. Makarov.

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Kozin, S.A., Cheglakov, I.B., Ovsepyan, A.A. et al. Peripherally Applied Synthetic Peptide isoAsp7-Aβ(1-42) Triggers Cerebral β-Amyloidosis. Neurotox Res 24, 370–376 (2013). https://doi.org/10.1007/s12640-013-9399-y

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  • DOI: https://doi.org/10.1007/s12640-013-9399-y

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