PMID- 22160221
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20211203
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 18
IP  - 1
DP  - 2012 Mar 30
TI  - Hematopoietic CC-chemokine receptor 2 (CCR2) competent cells are protective for 
      the cognitive impairments and amyloid pathology in a transgenic mouse model of 
      Alzheimer's disease.
PG  - 297-313
LID - 10.2119/molmed.2011.00306 [doi]
AB  - Monocytes emigrate from bone marrow, can infiltrate into brain, differentiate 
      into microglia and clear amyloid beta (Abeta) from the brain of mouse models of 
      Alzheimer's disease (AD). Here we show that these mechanisms specifically require 
      CC-chemokine receptor 2 (CCR2) expression in bone marrow cells (BMCs). Disease 
      progression was exacerbated in APP(Swe)/PS1 mice (transgenic mice expressing a 
      chimeric amyloid precursor protein [APPSwe] and human presenilin 1 [PS1]) 
      harboring CCR2-deficient BMCs. Indeed, transplantation of CCR2-deficient BMCs 
      enhanced the mnesic deficit and increased the amount of soluble Abeta and expression 
      of transforming growth factor (TGF)-beta1 and TGF-beta receptors. By contrast, 
      transplantation of wild-type bone marrow stem cells restored memory capacities 
      and diminished soluble Abeta accumulation in APP(Swe)/PS1 and APP(Swe)/PS1/CCR2(-)/(-) 
      mice. Finally, gene therapy using a lentivirus-expressing CCR2 transgene in BMCs 
      prevented cognitive decline in this mouse model of AD. Injection of CCR2 
      lentiviruses restored CCR2 expression and functions in monocytes. The presence of 
      these cells in the brain of non-irradiated APP(Swe)/PS1/CCR2(-)/(-) mice supports the 
      concept that they can be used as gene vehicles for AD. Decreased CCR2 expression 
      in bone marrow-derived microglia may therefore play a major role in the etiology 
      of this neurodegenerative disease.
FAU - Naert, Gaelle
AU  - Naert G
AD  - Laboratory of Endocrinology and Genomics, Centre Hospitalier de l'Universite 
      Laval-CHUL Research Center and Department of Molecular Medicine, Faculty of 
      Medicine, Laval University, Quebec, Canada.
FAU - Rivest, Serge
AU  - Rivest S
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120330
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
MH  - Alzheimer Disease/*metabolism/pathology/physiopathology
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Avoidance Learning
MH  - Brain/metabolism/pathology
MH  - Cognition Disorders/*metabolism/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Hematopoietic Stem Cells/*metabolism
MH  - Male
MH  - Memory
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Plaque, Amyloid
MH  - Protein Serine-Threonine Kinases/genetics
MH  - RNA, Messenger/metabolism
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, CCR2/*metabolism
MH  - Receptors, Transforming Growth Factor beta/genetics
MH  - Transforming Growth Factor beta1/genetics
PMC - PMC3327578
EDAT- 2011/12/14 06:00
MHDA- 2012/09/05 06:00
PMCR- 2011/11/29
CRDT- 2011/12/14 06:00
PHST- 2011/08/22 00:00 [received]
PHST- 2011/11/28 00:00 [accepted]
PHST- 2011/12/14 06:00 [entrez]
PHST- 2011/12/14 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
PHST- 2011/11/29 00:00 [pmc-release]
AID - molmed.2011.00306 [pii]
AID - 11_306_naert [pii]
AID - 10.2119/molmed.2011.00306 [doi]
PST - epublish
SO  - Mol Med. 2012 Mar 30;18(1):297-313. doi: 10.2119/molmed.2011.00306.