Alzforum webinar m heneka 20 03 2013

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Presentation made by Dr. Michael Heneka at the Alzheimer Research Forum Live Webinar of March 20, 2013 - http://www.alzforum.org/res/for/journal/detail.asp?liveID=209

Presentation made by Dr. Michael Heneka at the Alzheimer Research Forum Live Webinar of March 20, 2013 - http://www.alzforum.org/res/for/journal/detail.asp?liveID=209

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  • 1. Impact of Locus Coeruleus Degeneration in Alzheimer´s DiseaseMichael T. HenekaClincal Neuroscience Unit, University of Bonn andGerman center for Neurodegenerative DiseaseAlzforum, 20.03.2013
  • 2. Anatomy and function
  • 3. LC pathology in ADCON AD
  • 4. Aggravating spatial memory dysfunction 6 *** 3.5 ## *** reference memory errors working memory errors 3.0 ### 4 ** 2.5 2.0 ** 1.5 2 1.0 0.5 0 0.0 on tg n on 4 4 4 4 tg n sp sp sp sp o o t-c -c t-c -c t-d -d t-d -d tg tg w w w wdsp4 – induced LC degeneration in APP23 mice Heneka et al. J.Neurosci. , 2006
  • 5. Social memory dysfunction• Mice were habituated to the apparatus for 4 days.• A male mouse was presented for 5 minutes at the test day.• One hour later the same animal was represented.
  • 6. Ear2 ko (LC loss) vs DBH ko (NA loss) Hammerschmidt et al. Biol.Psychiatry, 2012
  • 7. Effects on synaptic plasticity
  • 8. L-threo-DOPS restores NE in the cortex and hippocampus Thomas et al. J.Neurochem. 1998 Heneka et al. PNAS 2010
  • 9. Behavioural improvement by L-threo DOPS
  • 10. Modulation of the synaptosome
  • 11. Partial protection of β-CaMKIIpThr286
  • 12. SummaryLocus ceruleus degeneration represents an early event in ADLoss of LC and NE in LC projection areas may cause early memorydysfunctionIF EE mediated effects are mediated by LC derived NA – can they beexpected in AD patients?Could EE/cognitive strategies slow disease progression more effectivelywhen patients receive NA substitution by L-threo DOPS?What´s the cause of LC degeneration and does EE delay/prevent it?