Marco Colonna Webinar July 2014

4,756 views

Published on

Webinar presentation made by Dr. Marco Colonna, July 8, 2014 http://www.alzforum.org/webinars/mutations-impair-trem2-maturation-processing-and-microglial-phagocytosis

Published in: Health & Medicine, Education
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
4,756
On SlideShare
0
From Embeds
0
Number of Embeds
3,768
Actions
Shares
0
Downloads
4
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Marco Colonna Webinar July 2014

  1. 1. Potential mechanisms by which TREM2 deficiency facilitates neurodegeneration Marco Colonna Washington University School of Medicine in St Louis
  2. 2. 1. Defect of microglia response
  3. 3. Defect of microglia response in 3-month old APPPS1-21 mice
  4. 4. Decreased plaque-associated microglia in TREM2 heterozygote mice Alexa568-HJ3.4- stained plaque GFP-expressing microgliaTREM2 Het TREM2 WT
  5. 5. • No impact of TREM2 haploinsufficiency on Aβ plaque deposition in 3-month old APPPS1-21 mice • No impact of TREM2 haploinsufficiency on Aβ-induced inflammatory milieu
  6. 6. 2. Defect of microglia survival
  7. 7. Reduced survival of DAP12-/- macrophages during in vitro culture WT DAP12-/- Propidium iodide staining CSF-1 Otero, Turnbull, Poliani et al Nat Immunol. 2009;10:734
  8. 8. Decreased microglia numbers and apoptotic morphology in 10 month-old DAP12-/- mice Basal ganglia Spinal cord WT DAP12-/-
  9. 9. 3. Excessive microglial inflammatory response
  10. 10. TREM-2 deficiency augments TNF-α and IL-6 responses to LPS, Zymosan and CpG Turnbull et al. J Immunol. 2006;177:3520
  11. 11. Is TREM2 inhibiting microglia inflammatory response to Aβ? Aβ LDLRApoE lysosome TNF-α IL-6 Aβ Aβ TREM2 DAP12
  12. 12. Acknowledgments Luigi Poliani Elena Fontana William Vermi Cristina Rossini Fabio Facchetti University of Brescia John Cirrito Jessica Restivo Todd Davis Katherine Young Jason Ulrich David Holtzman Alison Goate Carlos Cruchaga David Brody Rachel Smith Laura Piccio David Wozniak Funding: ADRC LIFA Lilly innovation fellowship program Yaming Wang Yoshinori Yamanishi

×