Alzheimer disease (AD) is regarded as an
amyloidosis of the brain, and, therefore, the prevention/deletion of
beta amyloid deposition is one of the most promising target of the treatment. Particularly, immune-mediated strategy is now known as A beta vaccination, which is thought to be a highly feasible way being applicable to AD patients. The A beta vaccination was originated by Schenk et al. in 1999. Since active and passive immunization of
amyloid precursor
protein (APP) gene- transgenic mice showed significant reduction of
beta amyloid deposits in the brain and the immunized mice showed improvement in cognitive functions, clinical trials were performed in US and Europe. However, the trial was suspended, because about 6% of patients who received the
vaccine developed
meningoencephalitis probably mediated by T cells reactive to A beta. Although the trial was halted, an autopsy case who had had the
meningoencephalitis suggested the disappearance of
senile plaques (Nicoll et al., 2003). Moreover, patients who developed
antibodies that recognize
senile plaques by immunohistochemistry showed significantly milder decline of cognitive functions than those who did not (Hock et al., 2003). Here, we report a safe and effective oral
vaccine using adeno-associated virus vector carrying A beta
cDNA tested in tg2576 mice.