Imaging of amyloid-β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy (original) (raw)

Nature Medicine volume 7, pages 369–372 (2001)Cite this article

Alzheimer disease (AD) can be diagnosed with certainty only post-mortem, by histologically demonstrating insoluble aggregates of amyloid-β peptide, called senile plaques1,2,3,4. Direct imaging of these lesions in the living brain would revolutionize early diagnosis of AD. Such imaging would also provide a powerful approach to monitor effects of putative anti-amyloid-β agents. However, the plaques are far too small to detect by conventional imaging techniques. The goal of this study was to develop novel imaging approaches, using in vivo multiphoton microscopy, to image senile plaques in PDAPP transgenic mice, which express a mutant human amyloid-β precursor protein and accumulate amyloid-β deposits5,6. We developed two robust methods: in vivo histology using the fluorescent histochemical dye thioflavine S, and in vivo immunofluorescence using labeled antibodies specific for amyloid-β. Immunization with amyloid-β peptide has been shown to prevent plaques in PDAPP mice7. We used our imaging techniques to test the hypothesis that existing plaques can be cleared by immunotherapy.

Multiphoton microscopy in the live mouse

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Acknowledgements

This work was supported by grants from the National Institute on Aging (AG08487, P01AG15453 and T32GM07753), and support from the Alzheimer Association and the Walters Family Foundation. An unrestricted gift from Elan Pharmaceuticals supported housing costs for the animals.

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Authors and Affiliations

  1. Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, USA
    Brian J. Bacskai, Stephen T. Kajdasz, Richard H. Christie, Cordelia Carter & Bradley T. Hyman
  2. Elan Pharmaceuticals, South San Francisco, California, USA
    Dora Games, Peter Seubert & Dale Schenk

Authors

  1. Brian J. Bacskai
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  2. Stephen T. Kajdasz
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  3. Richard H. Christie
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  4. Cordelia Carter
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  5. Dora Games
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  6. Peter Seubert
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  7. Dale Schenk
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  8. Bradley T. Hyman
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Corresponding author

Correspondence toBradley T. Hyman.

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Bacskai, B., Kajdasz, S., Christie, R. et al. Imaging of amyloid-β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy.Nat Med 7, 369–372 (2001). https://doi.org/10.1038/85525

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