Both active and passive immunization to eliminate amyloid plaques from the brain of patients with Alzheimer's disease (AD) have confirmed that amyloid beta (A beta) vaccination does not only result in clearance of A beta plaques but improves behavioral-cognitive deficits in animal models of AD. In the present study, the levels of naturally occurring serum antibodies against A were measured in Tg2576 mice at various ages using ELISA to determine the relationship between aging and the level of anti-A beta autoantibody. The level of anti-A beta antibody fell significantly at the age of 9 months, at the age when amyloid plaques started to appear in the brain of Tg2576 mice, and was persistently low thereafter. However, serum immunoglobulin (Ig) level was elevated in older transgenic mice compared with younger transgenic mice suggesting that the reduced level of anti-A beta autoantibody was not merely due to deterioration of the immune response in aged Tg2576 mice. (c) 2007 Elsevier Inc. All rights reserved.