|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
50
|
|
pubmed:dateCreated |
2010-12-16
|
|
pubmed:abstractText |
In Alzheimer's disease (AD), amyloid-? (A?) deposits are frequently surrounded by activated microglia but the precise role of these cells in disease progression remains unclear. The chemokine receptor CX3CR1 is selectively expressed in microglia and is thought to modulate their activity. To study the specific effects of microglia activation on amyloid pathology in vivo, we crossbred mice lacking CX3CR1 with the Alzheimer's mouse model CRND8. Surprisingly, we found that CX3CR1-deficient mice had lower brain levels of A?40 and A?42 and reduced amyloid deposits. Quantification of A? within microglia and time-lapse two-photon microscopy in live mice revealed that these cells were highly effective at the uptake of protofibrillar amyloid but were incapable of phagocytosis of fibrillar congophilic A?. CX3CR1 deletion was associated with increased phagocytic ability, which led to greater amyloid content within microglial phagolysosomes. Furthermore, CX3CR1-deficient mice had an increased number of microglia around individual plaques because of higher proliferative rates, which likely contributed to an overall greater phagocytic capacity. CX3CR1 deletion did not affect the degree of neuronal or synaptic damage around plaques despite increased microglia density. Our results demonstrate that microglia can regulate brain A? levels and plaque deposition via selective protofibrillar A? phagocytosis. Modulation of microglia activity and proliferation by CX3CR1 signaling may represent a therapeutic strategy for AD.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-10464339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-10805752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-11124423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-11279122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-11378249,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-11755009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-11910111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-12223540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-12230326,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-12490949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-12517955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-1376558,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-1414275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-15670831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-16148231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-16476660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-16541076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-16732273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-16984903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-17180163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-17351623,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-17897471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-17965659,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18026096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18026097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18378084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18417708,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18474729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18509040,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-18575457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-19234125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-1924295,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-19339619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-19388207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-19776284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-9242912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-9390561,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-9600986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/21159979-9724801
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
1529-2401
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
15
|
|
pubmed:volume |
30
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
17091-101
|
|
pubmed:dateRevised |
2011-10-17
|
|
pubmed:meshHeading |
pubmed-meshheading:21159979-Amyloid beta-Peptides,
pubmed-meshheading:21159979-Animals,
pubmed-meshheading:21159979-Brain,
pubmed-meshheading:21159979-Cell Proliferation,
pubmed-meshheading:21159979-Mice,
pubmed-meshheading:21159979-Mice, Knockout,
pubmed-meshheading:21159979-Microglia,
pubmed-meshheading:21159979-Neurons,
pubmed-meshheading:21159979-Peptide Fragments,
pubmed-meshheading:21159979-Phagocytosis,
pubmed-meshheading:21159979-Plaque, Amyloid,
pubmed-meshheading:21159979-Receptors, Chemokine,
pubmed-meshheading:21159979-Synapses
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-? phagocytosis.
|
|
pubmed:affiliation |
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
