Active immunization trial in Aβ42-injected P301L tau transgenic mice

Amyloid beta-peptide (A beta) 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 A is an initial and essential step in the pathogenesis of AD, and formation of NFT has been proposed to be caused by increased A beta levels. Several previous studies revealed that A beta plaque formation can be reduced or even prevented by active immunization with A beta preparations or by administration of A beta-specific antibodies. To assess the role of fibrillar preparations of A beta(42) in NFT formation, we previously performed intracerebral (i.c.) injections of A beta(42) into brains of NFT-forming P301L tau transgenic mice which 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 A beta(42). A beta(42)-specific titers were monitored and the mice injected i.c. with A beta(42). We found that i.c. injection of A beta(42) caused significant increases in NFT formation. However, this induction was not affected by active immunization despite high serum anti-A beta(42) titer levels and binding of anti-A beta(42) antibodies to the injected A beta(42) aggregates. We conclude that active immunization is not sufficient to prevent the effect of A beta(42) On tau aggregation in our model system. Further studies are required to determine whether modifications of our protocol could affect the A beta(42)-mediated induction of NFT formation. (c) 2005 Elsevier Inc. All rights reserved.