Document Detail


Immunization targeting a minor plaque constituent clears β-amyloid and rescues behavioral deficits in an Alzheimer's disease mouse model.
MedLine Citation:
PMID:  22608241     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although anti-human β-amyloid (Aβ) immunotherapy clears brain β-amyloid plaques in Alzheimer's disease (AD), targeting additional brain plaque constituents to promote clearance has not been attempted. Endogenous murine Aβ is a minor Aβ plaque component in amyloid precursor protein (APP) transgenic AD models, which we show is ∼3%-8% of the total accumulated Aβ in various human APP transgenic mice. Murine Aβ codeposits and colocalizes with human Aβ in amyloid plaques, and the two Aβ species coimmunoprecipitate together from brain extracts. In the human APP transgenic mouse model Tg2576, passive immunization for 8 weeks with a murine-Aβ-specific antibody reduced β-amyloid plaque pathology, robustly decreasing both murine and human Aβ levels. The immunized mice additionally showed improvements in two behavioral assays, odor habituation and nesting behavior. We conclude that passive anti-murine Aβ immunization clears Aβ plaque pathology--including the major human Aβ component--and decreases behavioral deficits, arguing that targeting minor endogenous brain plaque constituents can be beneficial, broadening the range of plaque-associated targets for AD therapeutics.
Authors:
Jose Morales-Corraliza; Stephen D Schmidt; Matthew J Mazzella; Jason D Berger; Donald A Wilson; Daniel W Wesson; Mathias Jucker; Efrat Levy; Ralph A Nixon; Paul M Mathews
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-18
Journal Detail:
Title:  Neurobiology of aging     Volume:  34     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-10-29     Completed Date:  2013-04-23     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  137-45     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / complications*,  genetics,  therapy*
Amyloid beta-Peptides / immunology*,  metabolism*
Amyloid beta-Protein Precursor / genetics
Animals
Antibodies, Monoclonal / therapeutic use*
Behavioral Symptoms* / etiology,  immunology,  therapy
Brain / metabolism*,  pathology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Humans
Mice
Mice, Transgenic
Mutation / genetics
Nesting Behavior / drug effects
Odors
Olfaction Disorders / etiology,  therapy
Presenilin-1 / genetics
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
AG017617/AG/NIA NIH HHS; AG037693/AG/NIA NIH HHS; DC003906/DC/NIDCD NIH HHS; NS045205/NS/NINDS NIH HHS; P01 AG017617/AG/NIA NIH HHS; R01 AG037693/AG/NIA NIH HHS; R01 DC003906/DC/NIDCD NIH HHS; R01 NS045205/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Antibodies, Monoclonal; 0/PSEN1 protein, human; 0/Presenilin-1
Comments/Corrections

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