title: Chronic anti-murine Aβ immunization preserves odor guided behaviors in an Alzheimer's β-amyloidosis model.
abstract: Olfaction is often impaired in Alzheimer's disease (AD) and is also dysfunctional in mouse models of the disease. We recently demonstrated that short-term passive anti-murine-Aβ immunization can rescue olfactory behavior in the Tg2576 mouse model overexpressing a human mutation of the amyloid precursor protein (APP) after β-amyloid deposition. Here we tested the ability to preserve normal olfactory behaviors by means of long-term passive anti-murine-Aβ immunization. Seven-month-old Tg2576 and non-transgenic littermate (NTg) mice were IP-injected biweekly with the m3.2 murine-Aβ-specific antibody until 16 mo of age when mice were tested in the odor habituation test. While Tg2576 mice treated with a control antibody showed elevations in odor investigation times and impaired odor habituation compared to NTg, olfactory behavior was preserved to NTg levels in m3.2-immunized Tg2576 mice. Immunized Tg2576 mice had significantly less β-amyloid immunolabeling in the olfactory bulb and entorhinal cortex, yet showed elevations in Thioflavin-S labeled plaques in the piriform cortex. No detectable changes in APP metabolite levels other than Aβ were found following m3.2 immunization. These results demonstrate efficacy of chronic, long-term anti-murine-Aβ m3.2 immunization in preserving normal odor-guided behaviors in a human APP Tg model. Further, these results provide mechanistic insights into olfactory dysfunction as a biomarker for AD by yielding evidence that focal reductions of Aβ may be sufficient to preserve olfaction.
authors.affiliation: Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, United States. dww53@case.edu
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Wesson
authors.forename: Jose
authors.initials: J
authors.lastname: Morales-Corraliza
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Mazzella
authors.forename: Donald A
authors.initials: DA
authors.lastname: Wilson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mathews
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D000857:Olfaction Disorders / Q000209:etiology* / Q000276:immunology / Q000628:therapy*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies