Immunization against beta-amyloid can reduce neuropathology and improve impaired behavior in transgenic mice. Whether antibodies against beta-amyloid are also effective in Alzheimer's disease (AD) is unknown. We have previously described the generation of antibodies against beta-amyloid in AD patients who received a prime and a booster immunization of aggregated Abeta42 in a placebo-controlled randomized trial. We developed a tissue amyloid plaque immunoreactivity (TAPIR) assay to determine the ability of the antibodies to react with bona fide beta-amyloid plaques in brain tissue of transgenic mice expressing AD-causing mutations.
By following patients over a one-year period, we found that patients who generated TAPIR-positive antibodies showed significantly slower rates of decline of cognitive functions and activities of daily living, and scored better on hippocampus-dependent memory tests as compared to patients without such antibodies. The beneficial clinical effects were also present in patients who had experienced transient episodes of immunization-related aseptic meningoencephalitis as an unwanted side effect of immunization. Our results show that the generation antibodies against β-amyloid in response to immunization can slow cognitive decline in patients with AD, suggesting that vaccination against beta-amyloid is a valuable option for the treatment of AD.