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P2–391: DNA beta‐amyloid 42 vaccination as a possible immunotherapy for Alzheimer's disease: The development of a beta‐amyloid 1–42 antibody‐producing pool of plasma cells in the bone marrow of immunized mice
Author(s) -
LambrachtWashington Doris,
Zacharias Tresa,
Fu Min,
Rosenberg Roger N
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.1040
Subject(s) - antibody , immune system , elispot , immunology , dna vaccination , spleen , biology , microbiology and biotechnology , plasma cell , bone marrow , epitope , virology , t cell , immunization
reproducible AD defects, and positions CVNmouse as the most complete AD model available.Methods:Wild-type and CVNmice were studied starting at age of 3 months. Behavioral battery included Open field, Barnesmaze, Radial arm water maze, and Contextual fear conditioning. At 3,6,9 and 12 months of age, tissue were collected for biochemical analysis. Immunohistochemical stainings for Ab1-40 and microglia were performed, and neuronal number was evaluated by CFV histological staining. MRI volumetric as well as spectroscopic (1H-MRS) analyses were performed.Results:CVNmice exhibited significant age-dependent behavioral deficits in Barnes maze, Radial arm water maze and Contextual fear conditioning. Robust biochemical changes, including increased number of dense amyloid plaques in hippocampus, thalamus and cortex, and increased levels of insoluble Ab subtypes were evident. Significant inflammatory response detected by Iba-1 and CD45 immunoreactive microglia was heavily condensed around the plaques in all brain regions studied. The number of viable neurons in hippocampus was significantly decreased in aged animals. In 1H-MRS several translational AD-related metabolic changes were detected. Conclusions: The new CVN mouse provides a more complete tool to study novel therapies targeted for treatment of AD. Several desired AD-related end-points are present in this mouse line making it a valuable model for drug development.