Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2

Molecular Neurodegeneration

David M Holtzman²  Marco Colonna³  Laura Piccio¹  Floy R Stewart¹  Hong Jiang¹  Thomas E Mahan¹  Alice Shen¹  Yaming Wang⁴  Mary Beth Finn¹  Jason D Ulrich¹ 

[1] Department of Neurology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA;Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, Saint Louis, Missouri 63110, USA;Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri 63110, USA;Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA

关键词: Amyloid β;    Microglia;    TREM2;    Alzheimer’s disease;   

Others  :  861471
DOI  :  10.1186/1750-1326-9-20

 received in 2014-03-09, accepted in 2014-05-20,  发布年份 2014

【 摘 要 】

Background

Recent genome-wide association studies linked variants in TREM2 to a strong increase in the odds of developing Alzheimer’s disease. The mechanism by which TREM2 influences the susceptibility to Alzheimer’s disease is currently unknown. TREM2 is expressed by microglia and is thought to regulate phagocytic and inflammatory microglial responses to brain pathology. Given that a single allele of variant TREM2, likely resulting in a loss of function, conferred an increased risk of developing Alzheimer’s disease, we tested whether loss of one functional trem2 allele would affect Aβ plaque deposition or the microglial response to Aβ pathology in APPPS1-21 mice.

Results

There was no significant difference in Aβ deposition in 3-month old or 7-month old APPPS1-21 mice expressing one or two copies of trem2. However, 3-month old mice with one copy of trem2 exhibited a marked decrease in the number and size of plaque-associated microglia. While there were no statistically significant differences in cytokine levels or markers of microglial activation in 3- or 7-month old animals, there were trends towards decreased expression of NOS2, C1qa, and IL1a in 3-month old TREM2^+/− vs. TREM2^+/+ mice.

Conclusions

Loss of a single copy of trem2 had no effect on Aβ pathology, but altered the morphological phenotype of plaque-associated microglia. These data suggest that TREM2 is important for the microglial response to Aβ deposition but that a 50% decrease inTREM2 expression does not affect Aβ plaque burden.

【 授权许可】

   
2014 Ulrich et al.; licensee BioMed Central Ltd.

【 图 表 】

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