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Active immunization trial in Abeta42-injected P301L tau transgenic mice


Kulic, L; Kurosinski, P; Chen, F; Tracy, J; Mohajeri, M H; Li, H; Nitsch, R M; Götz, J (2006). Active immunization trial in Abeta42-injected P301L tau transgenic mice. Neurobiology of Disease, 22(1):50-56.

Abstract

Amyloid beta-peptide (Abeta) 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 Abeta is an initial and essential step in the pathogenesis of AD, and formation of NFT has been proposed to be caused by increased Abeta levels. Several previous studies revealed that Abeta plaque formation can be reduced or even prevented by active immunization with Abeta preparations or by administration of Abeta-specific antibodies. To assess the role of fibrillar preparations of Abeta42 in NFT formation, we previously performed intracerebral (i.c.) injections of Abeta42 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 Abeta42. Abeta42-specific titers were monitored and the mice injected i.c. with Abeta42. We found that i.c. injection of Abeta42 caused significant increases in NFT formation. However, this induction was not affected by active immunization despite high serum anti-Abeta42 titer levels and binding of anti-Abeta42 antibodies to the injected Abeta42 aggregates. We conclude that active immunization is not sufficient to prevent the effect of Abeta42 on tau aggregation in our model system. Further studies are required to determine whether modifications of our protocol could affect the Abeta42-mediated induction of NFT formation.

Abstract

Amyloid beta-peptide (Abeta) 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 Abeta is an initial and essential step in the pathogenesis of AD, and formation of NFT has been proposed to be caused by increased Abeta levels. Several previous studies revealed that Abeta plaque formation can be reduced or even prevented by active immunization with Abeta preparations or by administration of Abeta-specific antibodies. To assess the role of fibrillar preparations of Abeta42 in NFT formation, we previously performed intracerebral (i.c.) injections of Abeta42 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 Abeta42. Abeta42-specific titers were monitored and the mice injected i.c. with Abeta42. We found that i.c. injection of Abeta42 caused significant increases in NFT formation. However, this induction was not affected by active immunization despite high serum anti-Abeta42 titer levels and binding of anti-Abeta42 antibodies to the injected Abeta42 aggregates. We conclude that active immunization is not sufficient to prevent the effect of Abeta42 on tau aggregation in our model system. Further studies are required to determine whether modifications of our protocol could affect the Abeta42-mediated induction of NFT formation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2006
Deposited On:05 Sep 2011 07:43
Last Modified:16 Aug 2016 10:14
Publisher:Elsevier
ISSN:0969-9961
Publisher DOI:https://doi.org/10.1016/j.nbd.2005.10.002
PubMed ID:16289870

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