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

1. Impact of Locus Coeruleus Degeneration
in Alzheimer´s Disease
Michael T. Heneka
Clincal Neuroscience Unit, University of Bonn and
German center for Neurodegenerative Disease
Alzforum, 20.03.2013

2. Anatomy and function

3. LC pathology in AD
CON 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
w
dsp4 – 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. Summary
Locus ceruleus degeneration represents an early event in AD
Loss of LC and NE in LC projection areas may cause early memory
dysfunction
IF EE mediated effects are mediated by LC derived NA – can they be
expected in AD patients?
Could EE/cognitive strategies slow disease progression more effectively
when patients receive NA substitution by L-threo DOPS?
What´s the cause of LC degeneration and does EE delay/prevent it?