Antibodies from a DNA peptide vaccination decrease the brain amyloid burden in a mouse model of Alzheimer's disease.
The neuropathology of Alzheimer's disease(AD) is characterized by the accumulation of amyloid peptide Abeta in the brain derived from proteolytic cleavage of the amyloid precursor protein (APP). Vaccination of mice with plasmid DNA coding for the human Abeta42 peptide together with low doses of preaggregated peptide induced antibodies with detectable titers after only 2 weeks. One serum was directed against the four aminoterminal amino acids DAEF and differs from previously described ones. Both immune sera and monoclonal antibodies solubilized preformed aggregates of Abeta42 in vitro and recognized amyloid plaques in brain sections of mice transgenic for human APP. Passive immunization of transgenic AD mice caused a significant and rapid reduction in brain amyloid plaques within 24 h. The combined DNA peptide vaccine may prove useful for active immunization with few inoculations and low peptide dose which may prevent the recently described inflammatory reactions inpatients. The monoclonal antibodies are applicable for passive immunization studies and may lead to a therapy of AD.
Schiltz
Jan G
JG
Institute if Medical Virology, University of Zurich, Gloriastrasse 30, 8028 Zurich, Switzerland.
Salzer
Ulrich
U
Mohajeri
M Hasan
MH
Franke
Daniel
D
Heinrich
Jochen
J
Pavlovic
Jovan
J
Wollmer
M Axel
MA
Nitsch
Roger M
RM
Moelling
Karin
K
D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry*; D004195:Disease Models, Animal; D000939:Epitopes; D006801:Humans; D007116:Immunization, Passive; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000494:pharmacology*
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010455:Peptides; D014614:Vaccines, Synthetic; D004247:DNA