PMID- 9422548
OWN - NLM
STAT- MEDLINE
DCOM- 19980130
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 152
IP  - 1
DP  - 1998 Jan
TI  - Microglial response to amyloid plaques in APPsw transgenic mice.
PG  - 307-17
AB  - Microglial activation is central to the inflammatory response in Alzheimer's 
      Disease (AD). A recently described mouse line, Tg(HuAPP695.K670N/M671L)2576, 
      expressing human amyloid precursor protein with a familial AD gene mutation, 
      age-related amyloid deposits, and memory deficits, was found to develop a 
      significant microglial response using Griffonia simplicifolia lectin or 
      phosphotyrosine probe to identify microglia Both Griffonia simplicifolia lectin 
      and phosphotyrosine staining showed increased numbers of intensely labeled, often 
      enlarged microglia clustered in and around plaques, consistent with microglial 
      activation related to beta-amyloid formation. Using quantitative image analysis 
      of coronal phosphotyrosine-immunostained sections, transgene-positive 10- to 
      16-month-old, hemizygous, hybrid Tg2576 (APPsw) animals showed significantly 
      increased microglial density and size in plaque-forming areas of hippocampus and 
      frontal, entorhinal, and occipital cortex. Quantitative analysis of microglia as 
      a function of distance from the center of plaques (double labeled for A beta 
      peptide and microglia) revealed highly significant, two- to fivefold elevations 
      in microglial number and area within plaques compared with neighboring regions. 
      Tg2576 beta-amyloid-plaque-forming mice should be a useful system for assessing 
      the consequences of the microglial-mediated inflammatory response to beta-amyloid 
      and developing anti-inflammatory therapeutic strategies for Alzheimer's disease. 
      These results provide the first quantitative link between beta-amyloid plaque 
      formation and microglial activation in an animal model with neuritic plaques and 
      memory deficits.
FAU - Frautschy, S A
AU  - Frautschy SA
AD  - Sepulveda Veterans Affairs Medical Center, GRECC, and Department of Medicine, 
      University of California, Los Angeles 91343, USA.
FAU - Yang, F
AU  - Yang F
FAU - Irrizarry, M
AU  - Irrizarry M
FAU - Hyman, B
AU  - Hyman B
FAU - Saido, T C
AU  - Saido TC
FAU - Hsiao, K
AU  - Hsiao K
FAU - Cole, G M
AU  - Cole GM
LA  - eng
GR  - AG10685/AG/NIA NIH HHS/United States
GR  - R01 AG016793/AG/NIA NIH HHS/United States
GR  - P50 AG016570/AG/NIA NIH HHS/United States
GR  - 5P50AG05131-13/AG/NIA NIH HHS/United States
GR  - R01 AG010685/AG/NIA NIH HHS/United States
GR  - R01 AG11125/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Amyloid beta-Protein Precursor)
SB  - IM
CIN - Am J Pathol. 1999 Jun;154(6):1627-31. PMID: 10362785
MH  - Alzheimer Disease/genetics
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Animals
MH  - Brain/pathology
MH  - Cell Count
MH  - Cell Line
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic/genetics/*physiology
MH  - Microglia/pathology/*physiology
MH  - Mutation
MH  - Plaque, Amyloid/pathology/*physiology
MH  - Transgenes/physiology
PMC - PMC1858113
EDAT- 1998/01/09 00:00
MHDA- 1998/01/09 00:01
PMCR- 1998/07/01
CRDT- 1998/01/09 00:00
PHST- 1998/01/09 00:00 [pubmed]
PHST- 1998/01/09 00:01 [medline]
PHST- 1998/01/09 00:00 [entrez]
PHST- 1998/07/01 00:00 [pmc-release]
PST - ppublish
SO  - Am J Pathol. 1998 Jan;152(1):307-17.