Age-related differences in the immune response to immunization with human Aβ42 peptide

Several studies show that plaque burden is resolved in young to middle-aged amyloid precursor protein transgenic mice after rigorous immunization with Abeta42 peptide. We determined if wildtype 20-month-old and 3-month-old animals could produce high-titer antibody against Abeta42 with a less strenuous immunization protocol. All treated young animals mounted a high-titer (20,000-50,000) response after two immunizations and sustained a strong response for 6 months following the initial treatment with Abeta42. However, 6 of 8 immunized aged animals did not respond after three immunizations. The 2 responding aged mice produced low-titer antibody (5,000-10,000), which rapidly declined to control levels within 5 weeks after the third immunization. Aged animals may require alternate strategies for successful vaccination, such as inclusion of stimulatory cytokines or better adjuvants. If tolerance to Abeta42 underlies the poor response observed in aged animals, then a mechanism to overcome this response will have to be investigated.