Active immunization trial in AB42-injected P301L tau transgenic mice

Amyloid B-peptide (AB) containing plaques and neurofibrillary tangles (NFT) are the two major histopathological hallmarks of Alzheimer’s disease (AD). According to the amyloid cascade hypothesis, deposition of AB is an initial and essential step in the pathogenesis of AD, and formation of NFT has been proposed to be caused by increased AB levels. Several previous studies revealed that AB plaque formation can be reduced or even prevented by active immunization with AB preparations or by administration of AB-specific antibodies. To assess the role of fibrillar preparations of AB42 in NFT formation, intracerebral (i.c.) injections of AB42 into brains of NFT-forming P301L tau transgenic mice caused significant increases in NFT numbers. To determine whether these increases in NFT can be blocked or reduced by active immunization, P301L tau mice were immunized with intraperitoneal injections of preaggregated AB42. AB42-specific titers were monitored and the mice injected i.c. with AB42.They found that i.c. injection of AB42 caused significant increases in NFT formation. However, this induction was not affected by active immunization despite high serum anti-AB42 titer levels and binding of anti-AB42 antibodies to the injected AB42 aggregates. They concluded that active immunization is not sufficient to prevent the effect of AB42 on tau aggregation in our model system. Further studies are required to determine whether modifications of their protocol could affect the AB42- mediated induction of NFT formation.