Document Detail


Chronic anti-murine Aβ immunization preserves odor guided behaviors in an Alzheimer's β-amyloidosis model.
MedLine Citation:
PMID:  23000537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Daniel W Wesson; Jose Morales-Corraliza; Matthew J Mazzella; Donald A Wilson; Paul M Mathews
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-20
Journal Detail:
Title:  Behavioural brain research     Volume:  237     ISSN:  1872-7549     ISO Abbreviation:  Behav. Brain Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-04-26     Revised Date:  2014-01-24    
Medline Journal Info:
Nlm Unique ID:  8004872     Medline TA:  Behav Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  96-102     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / complications*,  genetics
Amyloid beta-Peptides / immunology*,  metabolism*
Amyloid beta-Protein Precursor / genetics,  metabolism
Animals
Antibodies / therapeutic use*
Brain / drug effects,  immunology,  metabolism
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Transgenic
Mutation / genetics
Olfaction Disorders / etiology*,  immunology,  therapy*
Time Factors
Grant Support
ID/Acronym/Agency:
AG017617/AG/NIA NIH HHS; AG037693/AG/NIA NIH HHS; DC003906/DC/NIDCD NIH HHS; P01 AG017617/AG/NIA NIH HHS; R01 AG037693/AG/NIA NIH HHS; R01 DC003906/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Antibodies
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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