Document Detail

Review: experimental manipulations of microglia in mouse models of Alzheimer's pathology: activation reduces amyloid but hastens tau pathology.
MedLine Citation:
PMID:  23171029     Owner:  NLM     Status:  MEDLINE    
The inflammation hypothesis of Alzheimer's pathogenesis has directed much scientific effort towards ameliorating this disease. The development of mouse models of amyloid deposition permitted direct tests of the proposal that amyloid-activated microglia could cause neurodegeneration in vivo. Many approaches to manipulating microglial activation have been applied to these mouse models, and are the subject of this review. In general, these results do not support a direct neuricidal action of microglia in mouse amyloid models under any activation state. Some of the manipulations cause both a reduction in pathology and a reduction in microglial activation. However, at least for agents like ibuprofen, this outcome may result from a direct action on amyloid production, and a reduction in the microglial-provoking amyloid deposits, rather than from reduced microglial activation leading to a decline in amyloid deposition. Instead, a surprising number of the experimental manipulations which increase microglial activation lead to enhanced clearance of the amyloid deposits. Both the literature and new data presented here suggest that either classical or alternative activation of microglia can lead to enhanced amyloid clearance. However, a limited number of studies comparing the same treatments in amyloid-depositing vs. tau-depositing mice find the opposite effects. Treatments that benefit amyloid pathology accelerate tau pathology. This observation argues strongly that potential treatments be tested for impact on both amyloid and tau pathology before consideration of testing in humans.
D C Lee; J Rizer; J B Hunt; M-L B Selenica; M N Gordon; D Morgan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Neuropathology and applied neurobiology     Volume:  39     ISSN:  1365-2990     ISO Abbreviation:  Neuropathol. Appl. Neurobiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-24     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  7609829     Medline TA:  Neuropathol Appl Neurobiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  69-85     Citation Subset:  IM    
Copyright Information:
© 2012 British Neuropathological Society.
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MeSH Terms
Alzheimer Disease / immunology,  metabolism,  pathology*
Amyloid beta-Peptides / metabolism
Disease Models, Animal
Microglia / immunology,  metabolism,  pathology*
Plaque, Amyloid / immunology,  metabolism,  pathology*
tau Proteins / metabolism*
Grant Support
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/tau Proteins

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