alzforum webinar m heneka 20 03 2013
DESCRIPTION
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=209TRANSCRIPT
Impact of Locus Coeruleus Degenerationin Alzheimer´s Disease
Michael T. HenekaClincal Neuroscience Unit, University of Bonn andGerman center for Neurodegenerative Disease
Alzforum, 20.03.2013
Anatomy and function
LC pathology in AD
CON AD
Aggravating spatial memory dysfunction
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Heneka et al. J.Neurosci. , 2006
dsp4 – induced LC degeneration in APP23 mice
• Mice were habituated to theapparatus for 4 days.
• A male mouse was presentedfor 5 minutes at the test day.
• One hour later the sameanimal was represented.
Social memory dysfunction
Ear2 ko (LC loss) vs DBH ko (NA loss)
Hammerschmidt et al. Biol.Psychiatry, 2012
Effects on synaptic plasticity
L-threo-DOPS restores NE in the cortex andhippocampus
Thomas et al. J.Neurochem. 1998Heneka et al. PNAS 2010
Behavioural improvement by L-threo DOPS
Modulation of the synaptosome
Partial protection of β-CaMKIIpThr286
Summary
Locus ceruleus degeneration represents an early event in AD
Loss of LC and NE in LC projection areas may cause early memorydysfunction
IF 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?