Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse (original) (raw)

• Letter
• Published: 08 July 1999
• Robin Barbour1,
• Whitney Dunn1,
• Grace Gordon1,
• Henry Grajeda1,
• Teresa Guido1,
• Kang Hu1,
• Jiping Huang1,
• Kelly Johnson-Wood1,
• Karen Khan1,
• Dora Kholodenko1,
• Mike Lee1,
• Zhenmei Liao1,
• Ivan Lieberburg1,
• Ruth Motter1,
• Linda Mutter1,
• Ferdie Soriano1,
• George Shopp1,
• Nicki Vasquez1,
• Christopher Vandevert1,
• Shannan Walker1,
• Mark Wogulis1,
• Ted Yednock1,
• Dora Games1 &
• …
• Peter Seubert1

Nature volume 400, pages 173–177 (1999)Cite this article

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Abstract

Amyloid-β peptide (Aβ) seems to have a central role in the neuropathology of Alzheimer's disease (AD)1. Familial forms of the disease have been linked to mutations in the amyloid precursor protein (APP) and the presenilin genes2,3. Disease-linked mutations in these genes result in increased production of the 42-amino-acid form of the peptide (Aβ42)4,5,6,7,8, which is the predominant form found in the amyloid plaques of Alzheimer's disease9,10. The PDAPP transgenic mouse, which overexpresses mutant human APP (in which the amino acid at position 717 is phenylalanine instead of the normal valine), progressively develops many of the neuropathological hallmarks of Alzheimer's disease in an age- and brain-region-dependent manner11,12. In the present study, transgenic animals were immunized with Aβ42, either before the onset of AD-type neuropathologies (at 6 weeks of age) or at an older age (11 months), when amyloid-β deposition and several of the subsequent neuropathological changes were well established. We report that immunization of the young animals essentially prevented the development of β-amyloid-plaque formation, neuritic dystrophy and astrogliosis. Treatment of the older animals also markedly reduced the extent and progression of these AD-like neuropathologies. Our results raise the possibility that immunization with amyloid-β may be effective in preventing and treating Alzheimer's disease.

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Acknowledgements

We thank Rae Lyn Burke for helpful comments.

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Authors and Affiliations

1. Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, 94080, California, USA
   Dale Schenk, Robin Barbour, Whitney Dunn, Grace Gordon, Henry Grajeda, Teresa Guido, Kang Hu, Jiping Huang, Kelly Johnson-Wood, Karen Khan, Dora Kholodenko, Mike Lee, Zhenmei Liao, Ivan Lieberburg, Ruth Motter, Linda Mutter, Ferdie Soriano, George Shopp, Nicki Vasquez, Christopher Vandevert, Shannan Walker, Mark Wogulis, Ted Yednock, Dora Games & Peter Seubert

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1. Dale Schenk
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2. Robin Barbour
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3. Whitney Dunn
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4. Grace Gordon
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5. Henry Grajeda
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6. Teresa Guido
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7. Kang Hu
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8. Jiping Huang
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9. Kelly Johnson-Wood
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10. Karen Khan
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11. Dora Kholodenko
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12. Mike Lee
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13. Zhenmei Liao
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14. Ivan Lieberburg
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15. Ruth Motter
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16. Linda Mutter
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17. Ferdie Soriano
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18. George Shopp
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19. Nicki Vasquez
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20. Christopher Vandevert
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21. Shannan Walker
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22. Mark Wogulis
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23. Ted Yednock
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24. Dora Games
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25. Peter Seubert
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Correspondence toDale Schenk.

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Schenk, D., Barbour, R., Dunn, W. et al. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse.Nature 400, 173–177 (1999). https://doi.org/10.1038/22124

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• Received: 06 April 1999
• Accepted: 05 May 1999
• Issue Date: 08 July 1999
• DOI: https://doi.org/10.1038/22124

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