Transcript Annual meeting of the COST ACTION CM1103

Annual meeting of the COST ACTION CM1103
Neuropathology and neuropharmacology of monoaminergic system
Bordeaux, 8-10 Oct 2014
Pathogenesis and early diagnosis of
Alzheimer’s disease: involvement of
the monoaminergic system
Mirjana Babić, mag.biol.mol.
Laboratory for Developmental Neuropathology
Croatian Institute for Brain Research
1. Involvement of the monoaminergic system in
pathogenesis of Alzheimer’s disease
Andreasson et al., 2007.
Does Aβ pathology precedes tau pathology?
How are monoaminergic nuclei involved in this
process?
1)
Šimić et al., 2014.
2) The early occurrence of behavioral, and
psychological symptoms of dementia suggests
brainstem involvement, and more specifically of the
serotonergic nuclei.
Šimić et al., 2009.
3) Plaque formation in the brain of transgenic mouse
model (APPswe/PS1DE9 ) of AD causes the
deterioration of sleep–wake cycle
lesions of the raphe nuclei cause insomnia
Roh et al., 2012.
4) exposure to inorganic mercury, bismuth and silver
can lead to AD-like pathology in noradrenergic locus
coeruleus neurons
spreads to neighbouring
serotonergic dorsal raphe neurons
locus coeruleus neurons
2. Monoamine metabolites in early
diagnosis of Alzheimer’s disease
Decreased in CSF
homovanilic acid
5-hydroxyindoleacetic
acid (5HIAA)
dihydroxyphenylacetic
acid
monoamine synthesis
cofactor biopterin
serotonin
Increased in CSF
Kawakatsu et al., 1990 Zubenko et al., 1986
Martignoni et al., 1991 van der Cammen et al.,
Blennow et al., 1992
2006
Parnetti et al., 1992
Sjogren et al., 1998
Unchanged in CSF
Sheline et al., 1998
Stuerenburg et al.,
2004 Parnetti et al.,
1992
Volicer et al., 1985
5-hydroxytryptophan
noradrenaline
Sjogren et al., 1998
Toghi et al., 1992
Blennow et al., 1992
3-methoxy-4hydroxyphenylglycol
• Controversial results of the studies on CSF monoamine
metabolites in AD patients
Core CSF biomarkers
Aβ1-42
T-tau
P-tau181
Novel CSF biomarkers
P-tau199
P-tau231
VILIP-1
Noninvasively measured potential AD biomarkers
Laczo et al., 2009.
Measurement od event-related potentials.
• Components of event-related potentials (reaction times and P300
amplitude) differentiated two groups of MCI patients with pathological and
normal levels of p-tau199 and VILIP-1.
http://alzbiotrack.hiim.hr/
Croatian Science Foundation