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

• Published in: Nature (London) 2000-12, Vol.408 (6815), p.982-985
• Main Authors: Morgan, Dave, Diamond, David M, Gottschall, Paul E, Ugen, Kenneth E, Dickey, Chad, Hardy, John, Duff, Karen, Jantzen, Paul, DiCarlo, Giovanni, Wilcock, Donna, Connor, Karen, Hatcher, Jaime, Hope, Caroline, Gordon, Marcia, Arendash, Gary W
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer Disease - prevention & control; Amyloid beta-Peptides - administration & dosage; Animals; Antibodies - analysis; Antibodies - immunology; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Frontal Lobe - pathology; Humanities and Social Sciences; Humans; Immunohistochemistry; letter; Male; Maze Learning; Medical sciences; Memory Disorders - etiology; Memory Disorders - prevention & control; Mice; Mice, Transgenic; multidisciplinary; Neurology; Peptide Fragments - administration & dosage; Plaque, Amyloid - pathology; Science; Science (multidisciplinary); Vaccination
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35050116

Vaccinations with amyloid-β peptide (AB) 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 Aβ 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 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.