The cerebral accumulation of beta-amyloid (Abeta) is a pathological hallmark of Alzheimer's disease (AD). Abeta vaccination or anti-Abeta specific antibodies may be a possible therapeutic option for AD. Previously, we demonstrated variation in the humoral response between B6D2F1 and C57BL/6 during short term (14 weeks) Abeta immunization. In the present study, we determined the humoral and cellular immune responses in these same mouse strains to a longer period of Abeta vaccination and further refined the major B cell epitope to Ass1-7. B6D2F1 mice generated a greater humoral and Th1 immune response versus C57BL/6 mice. Immunization with 25 microg Abeta produced a greater T cell response in B6D2F1 mice compared to 50 or 100 microg Abeta but resulted in comparable humoral immunity. Thus, Abeta vaccination is affected by the genetic background and amount of Abeta peptide used as immunogen. These data may help explain some differences observed in Abeta immunization studies in mice of various genetic backgrounds and aid in the design of Abeta vaccines.