Document Detail


Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice.
MedLine Citation:
PMID:  23047754     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alzheimer's disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4-9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment is delayed considerably in outcrossed AβPP/PS1 mice relative to inbred mice on a C57BL/6 background. While inbred AβPP/PS1 mice develop deficits in radial-arm water maze performance and novel object recognition as early as 8 months, outcrossed AβPP/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred AβPP/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed AβPP/PS1 mice of the same age. Surprisingly, inbred AβPP/PS1 mice at 8 months have low plaque burden, suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of AβPP processing revealed that elevated levels of soluble Aβ correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and AβPP processing are sensitive to genetic differences between mouse strains.
Authors:
Brian A Couch; Meghan E Kerrisk; Adam C Kaufman; Haakon B Nygaard; Stephen M Strittmatter; Anthony J Koleske
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of comparative neurology     Volume:  521     ISSN:  1096-9861     ISO Abbreviation:  J. Comp. Neurol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-21     Completed Date:  2013-10-29     Revised Date:  2014-04-25    
Medline Journal Info:
Nlm Unique ID:  0406041     Medline TA:  J Comp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1395-408     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Protein Precursor / genetics*
Animals
Animals, Outbred Strains
Female
Male
Maze Learning / physiology
Memory Disorders / genetics*,  pathology*
Mice
Mice, 129 Strain
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Transgenic
Plaque, Amyloid / genetics*,  pathology*
Presenilin-1 / genetics*
Protein Processing, Post-Translational / genetics
Grant Support
ID/Acronym/Agency:
AG034924/AG/NIA NIH HHS; CA133346/CA/NCI NIH HHS; NS39475/NS/NINDS NIH HHS; R01 AG034924/AG/NIA NIH HHS; R01 GM100411/GM/NIGMS NIH HHS; R01 NS039475/NS/NINDS NIH HHS; T32 GM007205/GM/NIGMS NIH HHS; T32 GM007223/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Presenilin-1
Comments/Corrections

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


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