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Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse


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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Figure 1: Reduction of Aβ burden in the hippocampus at 13 months of age in mice immunized with Aβ42.
Figure 2: Hippocampal Aβ deposition, neuritic plaque formation and cortical astrocytosis in PBS- and Aβ42-injected mice.
Figure 3: Quantitative image analysis of the cortical Aβ burden in older PBS- and Aβ-treated mice.
Figure 4: Reduction of cortical Aβ deposition in older PDAPP mice immunized with Aβ42.
Figure 5: Reduction of Aβ burden in the entorhinal and retrosplenial cortex of older PDAPP mice following Aβ injection.
Figure 6: Altered Aβ burden in the hippocampus of older Aβ42-treated mice.


  1. Hyman, B. T. New neuropathological criteria for Alzheimer disease. Arch. Neurol. 55, 1174–1176 (1998).

    Article  CAS  Google Scholar 

  2. Tanzi, R. E. et al. The gene defects responsible for familial Alzheimer's disease. Neurobiol. Dis. 3, 159–168 (1996).

    Article  CAS  Google Scholar 

  3. Hardy, J. New insights into the genetics of Alzheimer's disease. Ann. Med. 28, 255–258 (1996).

    Article  CAS  Google Scholar 

  4. Citron, M. et al. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360, 672–674 (1992).

    Article  ADS  CAS  Google Scholar 

  5. Scheuner, D. et al. Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Med. 2, 864–870 (1996).

    Article  CAS  Google Scholar 

  6. Suzuki, N. et al. An increased percentage of long amyloid β protein secreted by familial amyloid β protein precursor (β APP717) mutants. Science 264, 1336–1340 (1994).

    Article  ADS  CAS  Google Scholar 

  7. Citron, M. et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice. Nature Med. 3, 67–72 (1997).

    Article  CAS  Google Scholar 

  8. Borchelt, D. R. et al. Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17, 1005–1013 (1996).

    Article  CAS  Google Scholar 

  9. Iwatsubo, T. et al. Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron 13, 45–53 (1994).

    Article  CAS  Google Scholar 

  10. Lippa, C. F., Nee, L. E., Mori, H. refau>& St George-Hyslop, P. Aβ-42 deposition precedes other changes in PS-1 Alzheimer's disease. Lancet 352, 1117–1118 (1998).

    Article  CAS  Google Scholar 

  11. Games, D. et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373, 523–527 (1995).

    Article  ADS  CAS  Google Scholar 

  12. Johnson-Wood, K. et al. Amyloid precursor protein processing and Aβ42 deposition in a transgenic mouse model of Alzheimer disease. Proc. Natl Acad. Sci. USA 94, 1550–1555 (1997).

    Article  ADS  CAS  Google Scholar 

  13. Liang, J. S. et al. Evidence for local production of acute phase response apolipoprotein serum amyloid A in Alzheimer's disease brain. Neurosci. Lett. 225, 73–76 (1997).

    Article  CAS  Google Scholar 

  14. McGeer, E. G. refau>& McGeer, P. L. The role of the immune system in neurodegenerative disorders. Mov. Disorders 12, 855–858 (1997).

    Article  CAS  Google Scholar 

  15. Seubert, P. et al. Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids. Nature 359, 325–327 (1992).

    Article  ADS  CAS  Google Scholar 

  16. Seubert, P. et al. Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide. Nature 361, 260–263 (1993).

    Article  ADS  CAS  Google Scholar 

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We thank Rae Lyn Burke for helpful comments.

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Correspondence to Dale 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).

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