Article
Rifampicin decreases cerebral beta-amyloid accumulation in APP/PS1 mice
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Authors
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Anja Brenn
- Institute of Pathology, Neuropathology, Greifswald, Germany
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Markus Grube
- Institute of Pharmacology, Greifswald, Germany
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Gabriele Jedlitschky
- Institute of Pharmacology, Greifswald, Gibraltar
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Susann Leupold
- Institute of Pathology, Neuropathology, Greifswald, Germany
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Barbara Strohmier
- Institute of Pathology, Neuropathology, Greifswald, Germany; Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany
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Markus Keller
- Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany
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Martin Eiden
- Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany
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Martin H. Groschup
- Friedrich-Loeffler-Institute, Institute for Novel and Emerging Infectious Diseases, Greifswald-Insel Riems, Germany
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Silke Vogelgesang
- Institute of Pathology, Neuropathology, Greifswald, Germany
| Published: | September 11, 2012 |
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Outline
Text
Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia and is characterized by the cerebral accumulation of beta-amyloid (Aβ) peptides. There is a substantial need for new therapies that modify the progression or prevent the onset of disease.
The antibiotic rifampicin, which is widely used in the treatment of tuberculosis and leprosy, was shown to inhibit the aggregation and fibril formation of synthetic Aβ peptides in a dose-dependent manner at reasonable concentrations in vitro. Furthermore, rifampicin was found to prevent Aβ-induced neurotoxicity on rat pheochromocytoma (PC12) cells. Recently, it was reported that three-month treatment with rifampicin showed a positive influence on cognitive function in patients with mild-to-moderate and AD dementia. Thus, rifampicin may have therapeutic potential in the treatment of AD.
Methods: To clarify the effect of rifampicin on the accumulation of Aβ in the brain, rifampicin was mixed with commercially available mouse diet (250 mg/kg) and was fed to 30 day-old male C57BL/6J-APP/PS1+/- mice over a period of 60 or 120 days (n=20), respectively. Twenty age-matched male C57BL/6J-APP/PS1+/- mice receiving a rifampicin-free diet served as controls. Immunohistochemical examination of brain tissue was performed using Aβ(1-40)- and Aβ(1-42)-specific antibodies. Furthermore, Aβ accumulation was determined using ELISA.
Results: Mice receiving rifampicin showed no differences in the levels of aggregated Aβ(1-40) and Aβ(1-42) after treatment for 60 days. However, soluble Aβ(1-42) was significantly reduced in the rifampicin-treated group (p=0.0058). Furthermore, 120 days after rifampicin administration cortical Aβ(1-40)-positive plaque numbers as well as the soluble Aβ(1-40) fraction was significantly decreased (p=0.013 or p=0.019, respectively). The number of Aβ(1-42)-positive plaques also was diminished, but this effect failed to reach statistical significance.
Conclusion: Our results show a reduced accumulation of Aβ in the brains of C57BL/6J-APP/PS1+/- mice after long-term administration of rifampicin. The mechanism of this effect is not fully understood, but it is worth investigating the possibility that rifampicin could protect the brain from Aβ accumulation, and thus could impede the progression of AD.
