Active immunization trial in Abeta42-injected P301L tau transgenic mice.
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.
Kulic
Luka
L
Division of Psychiatry Research, University of Zürich, August Forel Str. 1, 8008 Zürich, Switzerland.
Kurosinski
Pascal
P
Chen
Feng
F
Tracy
Jay
J
Mohajeri
M Hasan
MH
Li
Hong
H
Nitsch
Roger M
RM
Götz
Jürgen
J
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017211:Treatment Failure; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology*; D016875:tau Proteins / Q000235:genetics*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D014612:Vaccines; C075222:amyloid beta-protein (1-42); D016875:tau Proteins