1. 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

3. Does Aβ pathology precedes tau pathology?
1. Involvement of the monoaminergic system in pathogenesis of Alzheimer’s disease
Andreasson et al., 2007.
Does Aβ pathology precedes tau pathology?

4. How are monoaminergic nuclei involved in this process?

5. 1)
Šimić et al., 2014.

6. lesions of the raphe nuclei cause insomnia
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.

7. 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

8. 2. Monoamine metabolites in early diagnosis of Alzheimer’s disease
Decreased in CSF
Increased in CSF
Unchanged in CSF
homovanilic acid
Kawakatsu et al., 1990 Martignoni et al., 1991 Blennow et al., 1992 Parnetti et al., 1992
Sjogren et al., 1998
Zubenko et al., 1986
van der Cammen et al., 2006
Sheline et al., 1998
Stuerenburg et al., 2004 Parnetti et al., 1992
5-hydroxyindoleacetic acid (5HIAA)
dihydroxyphenylacetic acid
monoamine synthesis cofactor biopterin
serotonin
Volicer et al., 1985
5-hydroxytryptophan
noradrenaline
Toghi et al., 1992
Blennow et al., 1992
3-methoxy-4-hydroxyphenylglycol
Controversial results of the studies on CSF monoamine metabolites in AD patients

9. Core CSF biomarkers Novel CSF biomarkers
T-tau
P-tau181
Novel CSF biomarkers
P-tau231
VILIP-1
P-tau199

10. Noninvasively measured potential AD biomarkers
Laczo et al., 2009.
Measurement od event-related potentials.

11. 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.

12.
Croatian Science Foundation