PMID- 12612547
OWN - NLM
STAT- MEDLINE
DCOM- 20030530
LR  - 20220309
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 9
IP  - 4
DP  - 2003 Apr
TI  - Adult mouse astrocytes degrade amyloid-beta in vitro and in situ.
PG  - 453-7
AB  - Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized 
      by excessive deposition of amyloid-beta (Abeta) peptides in the brain. One of the 
      earliest neuropathological changes in AD is the accumulation of astrocytes at 
      sites of Abeta deposition, but the cause or significance of this cellular 
      response is unclear. Here we show that cultured adult mouse astrocytes migrate in 
      response to monocyte chemoattractant protein-1 (MCP-1), a chemokine present in AD 
      lesions, and cease migration upon interaction with immobilized Abeta(1-42). We 
      also show that astrocytes bind and degrade Abeta(1-42). Astrocytes plated on 
      Abeta-laden brain sections from a mouse model of AD associate with the Abeta 
      deposits and reduce overall Abeta levels in these sections. Our results suggest a 
      novel mechanism for the accumulation of astrocytes around Abeta deposits, 
      indicate a direct role for astrocytes in degradation of Abeta and implicate 
      deficits in astroglial clearance of Abeta in the pathogenesis of AD. Treatments 
      that increase removal of Abeta by astrocytes may therefore be a critical 
      mechanism to reduce the neurodegeneration associated with AD.
FAU - Wyss-Coray, Tony
AU  - Wyss-Coray T
AD  - Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care 
      System, Palo Alto, California, USA.
FAU - Loike, John D
AU  - Loike JD
FAU - Brionne, Thomas C
AU  - Brionne TC
FAU - Lu, Emily
AU  - Lu E
FAU - Anankov, Roman
AU  - Anankov R
FAU - Yan, Fengrong
AU  - Yan F
FAU - Silverstein, Samuel C
AU  - Silverstein SC
FAU - Husemann, Jens
AU  - Husemann J
LA  - eng
GR  - AG-08702/AG/NIA NIH HHS/United States
GR  - AG-15871/AG/NIA NIH HHS/United States
GR  - AG-19772/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030303
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (10-43))
SB  - IM
CIN - Trends Mol Med. 2003 Jul;9(7):279-80. PMID: 12900212
CIN - Trends Mol Med. 2003 Jul;9(7):281-2. PMID: 12900213
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Astrocytes/immunology/*metabolism
MH  - Cell Movement
MH  - Chemokine CCL2/pharmacology
MH  - Mice
MH  - Peptide Fragments/*metabolism
EDAT- 2003/03/04 04:00
MHDA- 2003/05/31 05:00
CRDT- 2003/03/04 04:00
PHST- 2002/11/20 00:00 [received]
PHST- 2003/02/05 00:00 [accepted]
PHST- 2003/03/04 04:00 [pubmed]
PHST- 2003/05/31 05:00 [medline]
PHST- 2003/03/04 04:00 [entrez]
AID - nm838 [pii]
AID - 10.1038/nm838 [doi]
PST - ppublish
SO  - Nat Med. 2003 Apr;9(4):453-7. doi: 10.1038/nm838. Epub 2003 Mar 3.