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Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease

Simard, Alain R; Soulet, Denis LU ; Gowing, Genevieve; Julien, Jean-Pierre and Rivest, Serge (2006) In Neuron 49(4). p.489-502
Abstract
Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific... (More)
Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
PROTEINS, HUMDISEASE, STEMCELL
in
Neuron
volume
49
issue
4
pages
489 - 502
publisher
Cell Press
external identifiers
  • pmid:16476660
  • scopus:32344440522
ISSN
0896-6273
DOI
10.1016/j.neuron.2006.01.022
language
English
LU publication?
yes
id
e140d98f-224d-4ab5-86ae-622f4f4e655c (old id 1137237)
date added to LUP
2008-06-03 13:07:06
date last changed
2019-10-13 03:36:23
@article{e140d98f-224d-4ab5-86ae-622f4f4e655c,
  abstract     = {Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques.},
  author       = {Simard, Alain R and Soulet, Denis and Gowing, Genevieve and Julien, Jean-Pierre and Rivest, Serge},
  issn         = {0896-6273},
  keyword      = {PROTEINS,HUMDISEASE,STEMCELL},
  language     = {eng},
  number       = {4},
  pages        = {489--502},
  publisher    = {Cell Press},
  series       = {Neuron},
  title        = {Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease},
  url          = {http://dx.doi.org/10.1016/j.neuron.2006.01.022},
  volume       = {49},
  year         = {2006},
}