[Treatment of Alzheimer disease: A beta vaccine]

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.