A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease.
Vaccinations with amyloid-beta peptide (A beta) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease. To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A beta vaccination in a different transgenic model for Alzheimer's disease in which mice develop learning deficits as amyloid accumulates. Here we show that vaccination with A beta 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 A beta-vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The A beta-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.
Morgan
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Department of Pharmacology, University of South Florida, Tampa 33612, USA. dmorgan@hsc.usf.edu
Diamond
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Gottschall
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Ugen
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Dickey
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Hardy
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Duff
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Jantzen
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DiCarlo
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Wilcock
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Connor
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Hatcher
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Hope
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Gordon
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Arendash
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D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage*; D058225:Plaque, Amyloid / Q000473:pathology; D014611:Vaccination
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)