Details

Autor(en) / Beteiligte

• Ulrich, Jason D
• Ulland, Tyler K
• Mahan, Thomas E
• Nyström, Sofie
• Nilsson, K Peter
• Song, Wilbur M
• Zhou, Yingyue
• Reinartz, Mariska
• Choi, Seulah
• Jiang, Hong
• Stewart, Floy R
• Anderson, Elise
• Wang, Yaming
• Colonna, Marco
• Holtzman, David M

Titel

ApoE facilitates the microglial response to amyloid plaque pathology

Ist Teil von

• The Journal of experimental medicine, 2018-04, Vol.215 (4), p.1047-1058

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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 that deficiency reduced fibrillar plaque deposition, consistent with previous studies. However, fibrillar plaques in -deficient mice exhibited a striking reduction in plaque compaction. Hyperspectral fluorescent imaging using luminescent conjugated oligothiophenes identified distinct Aβ morphotypes in -deficient mice. We also observed a significant reduction in fibrillar plaque-associated microgliosis and activated microglial gene expression in -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.