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

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Alzforum webinar m heneka 20 03 2013

  1. 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. 2. Anatomy and function
  3. 3. LC pathology in ADCON AD
  4. 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. 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. 6. Ear2 ko (LC loss) vs DBH ko (NA loss) Hammerschmidt et al. Biol.Psychiatry, 2012
  7. 7. Effects on synaptic plasticity
  8. 8. L-threo-DOPS restores NE in the cortex and hippocampus Thomas et al. J.Neurochem. 1998 Heneka et al. PNAS 2010
  9. 9. Behavioural improvement by L-threo DOPS
  10. 10. Modulation of the synaptosome
  11. 11. Partial protection of β-CaMKIIpThr286
  12. 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?

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