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

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.

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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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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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