[Vaccination therapy for Alzheimer's disease].

Alzheimer's disease is a neurodegenerative disorder characterized by senile plaques in the brain. In the senile plaques beta-amyloid is deposited and neuroinflammation due to innate immune responses against beta-amyloid is thought to cause degeneration of synapses and neural processes. In 1999 Dale Schenk et al. discovered that immunization of amyloid precursor protein (APP) transgenic mice with amyloid-beta protein (A-beta) reduces senile plaques and prevents new deposits of beta-amyloid. They also have found that antibodies to A-beta have similar effect. Since immunized mice showed improvement of cognitive functions, an active immunization method was tested in humans. However, the trial was halted because of side effect, subacute meningoencephalitis due to T-cell mediated autoimmune responses. We developed a safe oral A-beta vaccine using adeno-associated virus vector. When this vaccine was given once, antibodies were elevated well and high titers were kept for over 6 months. APP transgenic mice and old monkeys showed significant reduction of amyloid burden without any side effect. Since Th1 immune responses are suppressed in the gut immune system, this is a promising way to treat and prevent Alzheimer's disease.