Title |
ApoE facilitates the microglial response to amyloid plaque pathology
|
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Published in |
The Journal of Experimental Medicine, February 2018
|
DOI | 10.1084/jem.20171265 |
Pubmed ID | |
Authors |
Jason D. Ulrich, Tyler K. Ulland, Thomas E. Mahan, Sofie Nyström, K. Peter Nilsson, Wilbur M. Song, Yingyue Zhou, Mariska Reinartz, Seulah Choi, Hong Jiang, Floy R. Stewart, Elise Anderson, Yaming Wang, Marco Colonna, David M. Holtzman |
Abstract |
One of the hallmarks of Alzheimer's disease is the presence of extracellular diffuse and fibrillar plaques predominantly consisting of the amyloid-β (Aβ) peptide. Apolipoprotein E (ApoE) influences the deposition of amyloid pathology through affecting the clearance and aggregation of monomeric Aβ in the brain. In addition to influencing Aβ metabolism, increasing evidence suggests that apoE influences microglial function in neurodegenerative diseases. Here, we characterize the impact that apoE has on amyloid pathology and the innate immune response in APPPS1ΔE9 and APPPS1-21 transgenic mice. We report thatApoedeficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques inApoe-deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes inApoe-deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression inApoe-deficient mice, along with significant increases in dystrophic neurites around fibrillar plaques. Our results suggest that apoE is critical in stimulating the innate immune response to amyloid pathology. |
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