PMID- 11329064
OWN - NLM
STAT- MEDLINE
DCOM- 20010531
LR  - 20101118
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 7
IP  - 5
DP  - 2001 May
TI  - TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in 
      transgenic mice.
PG  - 612-8
AB  - Abnormal accumulation of the amyloid-beta peptide (Abeta) in the brain appears 
      crucial to pathogenesis in all forms of Alzheimer disease (AD), but the 
      underlying mechanisms in the sporadic forms of AD remain unknown. Transforming 
      growth factor beta1 (TGF-beta1), a key regulator of the brain's responses to 
      injury and inflammation, has been implicated in Abeta deposition in vivo. Here we 
      demonstrate that a modest increase in astroglial TGF-beta1 production in aged 
      transgenic mice expressing the human beta-amyloid precursor protein (hAPP) 
      results in a three-fold reduction in the number of parenchymal amyloid plaques, a 
      50% reduction in the overall Abeta load in the hippocampus and neocortex, and a 
      decrease in the number of dystrophic neurites. In mice expressing hAPP and 
      TGF-beta1, Abeta accumulated substantially in cerebral blood vessels, but not in 
      parenchymal plaques. In human cases of AD, Abeta immunoreactivity associated with 
      parenchymal plaques was inversely correlated with Abeta in blood vessels and 
      cortical TGF-beta1 mRNA levels. The reduction of parenchymal plaques in 
      hAPP/TGF-beta1 mice was associated with a strong activation of microglia and an 
      increase in inflammatory mediators. Recombinant TGF-beta1 stimulated Abeta 
      clearance in microglial cell cultures. These results demonstrate that TGF-beta1 
      is an important modifier of amyloid deposition in vivo and indicate that 
      TGF-beta1 might promote microglial processes that inhibit the accumulation of 
      Abeta in the brain parenchyma.
FAU - Wyss-Coray, T
AU  - Wyss-Coray T
AD  - Gladstone Institute of Neurological Disease, University of California, San 
      Francisco, California, USA. twysscoray@gladstone.ucsf.edu
FAU - Lin, C
AU  - Lin C
FAU - Yan, F
AU  - Yan F
FAU - Yu, G Q
AU  - Yu GQ
FAU - Rohde, M
AU  - Rohde M
FAU - McConlogue, L
AU  - McConlogue L
FAU - Masliah, E
AU  - Masliah E
FAU - Mucke, L
AU  - Mucke L
LA  - eng
SI  - GENBANK/M13177
SI  - GENBANK/M18194
SI  - GENBANK/M23703
SI  - GENBANK/M24914
SI  - GENBANK/X02812
SI  - GENBANK/X06989
GR  - AG-10689/AG/NIA NIH HHS/United States
GR  - AG-11385/AG/NIA NIH HHS/United States
GR  - AG-15871/AG/NIA NIH HHS/United States
GR  - AG-51131/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.
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
CIN - Nat Med. 2001 May;7(5):527-8. PMID: 11329045
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Blood Vessels/metabolism
MH  - Brain/metabolism/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Microglia/*metabolism
MH  - Molecular Sequence Data
MH  - Transforming Growth Factor beta/genetics/*physiology
MH  - Transforming Growth Factor beta1
EDAT- 2001/05/01 10:00
MHDA- 2001/06/02 10:01
CRDT- 2001/05/01 10:00
PHST- 2001/05/01 10:00 [pubmed]
PHST- 2001/06/02 10:01 [medline]
PHST- 2001/05/01 10:00 [entrez]
AID - 87945 [pii]
AID - 10.1038/87945 [doi]
PST - ppublish
SO  - Nat Med. 2001 May;7(5):612-8. doi: 10.1038/87945.