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Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease

Nature volume 408, pages 982–985 (2000)Cite this article

A Corrigendum to this article was published on 09 August 2001

Abstract

Vaccinations with amyloid-β peptide (AB) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease1. To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of Aβ vaccination in a different transgenic model for Alzheimer's disease in which mice develop learning deficits as amyloid accumulates2,3 . Here we show that vaccination with Aβ protects transgenic mice from the learning and age-related memory deficits that normally occur in this mouse model for Alzheimer's disease. During testing for potential deleterious effects of the vaccine, all mice performed superbly on the radial-arm water-maze test of working memory. Later, at an age when untreated transgenic mice show memory deficits, the Aβ-vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The Aβ-vaccinated mice also had a partial reduction in amyloid burden at the end of the study. This therapeutic approach may thus prevent and, possibly, treat Alzheimer's dementia.

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Figure 1: Radial-arm water-maze performance in vaccinated transgenic and nontransgenic mice.
Figure 2: Amyloid pathology in transgenic mice vaccinated with KLH or Aβ.
Figure 3: Measurement of amyloid histopathology after Aβ peptide immunization.

References

  1. Schenk, D. et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173–177 (1999).

    Article  ADS  CAS  Google Scholar 

  2. Gordon, M. N. et al. Correlation between cognitive deficits and Aβ deposits in transgenic APP+PS1 mice. Neurobiol. Aging (in the press).

  3. Arendash, G. W. et al. Progressive behavioral impairments in transgenic mice carrying both mutant APP and PS1 transgenes. Brain Res. (in the press).

  4. McGeer, E. G. & McGeer, P. L. The importance of inflammatory mechanisms in Alzheimer disease. Exp. Gerontol. 33, 371–378 (1998).

    Article  CAS  Google Scholar 

  5. Rogers, J. et al. Inflammation and Alzheimer's disease pathogenesis. Neurobiol. Aging 17, 681–686 (1996).

    Article  CAS  Google Scholar 

  6. Frautschy, S. A. Microglial response to amyloid plaques in APPsw transgenic mice. Am. J. Pathol. 152, 307–317 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Masliah, E. et al. Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease. J. Neurosci. 16, 5795–5811 (1996).

    Article  CAS  Google Scholar 

  8. Calhoun, M. E. et al. Neuron loss in APP transgenic mice. Nature 395, 755–756 (1998).

    Article  ADS  CAS  Google Scholar 

  9. Weiner, H. L. et al. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease. Ann. Neurol. 48, 567–579 (2000).

    Article  CAS  Google Scholar 

  10. Bard, F. et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med. 6, 916–919 (2000).

    Article  CAS  Google Scholar 

  11. Frenkel, D., Solomon, B. & Benhar, I. Modulation of Alzheimer's beta-amyloid neurotoxicity by site-directed single-chain antibody. J. Neuroimmunol. 106, 23–31 (2000).

    Article  CAS  Google Scholar 

  12. Holcomb, L. et al. Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nature Med. 4, 97–100 (1998).

    Article  CAS  Google Scholar 

  13. Holcomb, L. A. et al. Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: Lack of association with amyloid deposits. Behav. Gen. 29, 177–185 (1999).

    Article  CAS  Google Scholar 

  14. McGowan, E. et al. Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol. Dis. 6, 231–244 (1999).

    Article  CAS  Google Scholar 

  15. Mucke, L. et al. High level neuronal expression of Aβ1–42 in wild-type human amyloid precursor protein transgenic mice: Synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058 (2000).

    Article  CAS  Google Scholar 

  16. Hsiao, K. et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99–102 (1996).

    Article  ADS  CAS  Google Scholar 

  17. Duff, K. et al. Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383, 710–713 (1996).

    Article  ADS  CAS  Google Scholar 

  18. Diamond, D. M., Park, C. R., Heman, K. L. & Rose, G. M. Exposing rats to a predator impairs spatial working memory in the radial arm water maze. Hippocampus 9, 542–551 (1999).

    Article  CAS  Google Scholar 

  19. Gordon, M. N., Schreier, W. A., Ou, X., Holcomb, L. A. & Morgan, D. G. Exaggerated astrocyte reactivity after nigrostriatal deafferentation in the aged rat. J. Comp. Neurol. 388, 106–119 (1997).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank K. Hsiao-Ashe for sharing the Tg2576 mouse line. We thank R. Engelman and U. Owens for superb veterinary services in the maintenance of the transgenic colony. We thank I. Johnson for accounting services associated with the project. This work was supported by grants from the National Institute on Aging to M.G. and D.M., from the National Institute of Allergy and Infectious Disease and the National Heart Lung and Blood Institute to K.U., by the Benjamin Research Trust to D.M. and by an award from the University of South Florida Research Foundation.

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Authors and Affiliations

  1. Department of Pharmacology, Alzheimer Research Laboratory,

    Dave Morgan, Paul E. Gottschall, Paul Jantzen, Giovanni DiCarlo, Donna Wilcock, Karen Connor & Marcia Gordon

  2. Department of Psychology,

    David M. Diamond

  3. Department of Medical Microbiology and Immunology,

    Kenneth E. Ugen & Chad Dickey

  4. Alzheimer Research Laboratory, Department of Biology, University of South Florida, Tampa, 33612, Florida, USA

    Jaime Hatcher, Caroline Hope & Gary W. Arendash

  5. James A. Haley VA Center, Tampa, 33612, Florida, USA

    David M. Diamond

  6. Department of Pharmacology, Mayo Clinic, Jacksonville, 32224, Florida, USA

    John Hardy

  7. Nathan Kline Institute, Orangeburg, 10962, New York, USA

    Karen Duff

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  1. Dave Morgan
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Correspondence to Dave Morgan.

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Morgan, D., Diamond, D., Gottschall, P. et al. Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982–985 (2000). https://doi.org/10.1038/35050116

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