Presentation made by Terrence Town, PhD, at the December 12, 2012 webinar hosted by the Alzheimer Research Forum. http://www.alzforum.org/res/for/journal/detail.asp?liveID=207

1. Targeting ‘good’ neuroinflammation
in Alzheimer’s disease
Terrence Town, Ph.D.
Ben Winters Professor
of Regenerative Medicine
Regenerative Medicine Institute at
Cedars-Sinai Medical Center/UCLA
*NOTHING TO DISCLOSE

2. Alzheimer’s disease pathology
plaque
tangles neuron
Tan *, Town* et al.
Science 1999
Tan*, Town* et al.
Nat. Neurosci.
2002
Town et al. Nat. Med.
2008
microglia (innate immune cells)

3. Neuroinflammation in AD:
the good, the bad, and the ugly
• Retrospective epidemiology: inverse risk
relationship between NSAIDs and AD
• Primary prevention clinical trial (ADAPT): are
NSAIDs protective?
• Beneficial microgliosis – the Elan/Wyeth AN-1792
Aβ1-42 vaccine trial
• Contemporary view: different forms of neuro-
inflammation- some helpful, others deleterious

4. Reduced Aβ plaques after innate
immune TGF-β receptor inhibition
perfuse mice with PBS Alzheimer pathology
CC HC EC
Tg2576
crossed
Town et al., Nat. Med., 2008 scale bar denotes 100 µm

5. Gate et al., J. Neural Transm., 2010

6. Conclusions
• Blockade of macrophage anti-inflammatory
TGF-β signaling activates plaque clearance
• Deletion of a related key anti-inflammatory
molecule, IL-10, targets microglial Aβ clearance
• Promoting inflammation in IRAK-M knockouts
endorses microglial activation to clear Aβ
• These ‘good’ forms of neuroinflammation do not
appear to come at the cost of bystander
neurotoxicity

7. Acknowledgements
University of California
Eliezer Masliah, M.D.
Charles G. Glabe, Ph.D
Yale University
Tarek Fahmy, Ph.D.
Pasko Rakic, M.D., Ph.D.
Novartis Pharmaceuticals
Matthias Staufenbiel, Ph.D.
Town Lab, Cedars-Sinai/UCLA Ulf Neumann, Ph.D.
Kavon Rezai-Zadeh, Ph.D.
Altan Rentsendorj, Ph.D.
David Gate
Joshua J. Breunig, Ph.D.
Tara M. Weitz, Ph.D.
Marie-Victoire Guillot-Sestier, Ph.D.
Alzheimer’s Association (IIRG-0514993, ZEN-10-174633), Ellison Medical Foundation/AFAR Julie
Martin Mid-Career Award (M11472), NIH/NIA (AG029726), and NIH/NINDS (R01 NS076794)