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Letters to Nature

Nature 408, 982-985 (21 December 2000) | doi:10.1038/35050116; Received 21 August 2000; Accepted 7 November 2000

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

Dave Morgan1, David M. Diamond2,3, Paul E. Gottschall1, Kenneth E. Ugen4, Chad Dickey4, John Hardy5, Karen Duff6, Paul Jantzen1, Giovanni DiCarlo1, Donna Wilcock1, Karen Connor1, Jaime Hatcher7, Caroline Hope7, Marcia Gordon1 & Gary W. Arendash7

  1. Alzheimer Research Laboratory, Department of Pharmacology,
  2. Department of Psychology,
  3. Department of Medical Microbiology and Immunology,
  4. Alzheimer Research Laboratory, Department of Biology, University of South Florida, Tampa, Florida 33612, USA
  5. James A. Haley VA Center, Tampa, Florida 33612, USA
  6. Department of Pharmacology, Mayo Clinic, Jacksonville, Florida 32224, USA
  7. Nathan Kline Institute, Orangeburg, New York 10962, USA

Correspondence to: Dave Morgan1 Correspondence and requests for materials should be addressed to D. M. (e-mail: Email: dmorgan@hsc.usf.edu).

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Vaccinations with amyloid-beta 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 Abeta 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 Abeta 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 Abeta-vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The Abeta-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.

  1. Alzheimer Research Laboratory, Department of Pharmacology,
  2. Department of Psychology,
  3. Department of Medical Microbiology and Immunology,
  4. Alzheimer Research Laboratory, Department of Biology, University of South Florida, Tampa, Florida 33612, USA
  5. James A. Haley VA Center, Tampa, Florida 33612, USA
  6. Department of Pharmacology, Mayo Clinic, Jacksonville, Florida 32224, USA
  7. Nathan Kline Institute, Orangeburg, New York 10962, USA

Correspondence to: Dave Morgan1 Correspondence and requests for materials should be addressed to D. M. (e-mail: Email: dmorgan@hsc.usf.edu).