Annual meeting of the COST ACTION CM1103 Neuropathology and neuropharmacology of monoaminergic system

Bordeaux, 8-10 Oct 2014

Mirjana Babić, mag.biol.mol.Laboratory for Developmental Neuropathology

Croatian Institute for Brain Research

Pathogenesis and early diagnosis of Alzheimer’s disease: involvement of

the monoaminergic system

Does Aβ pathology precedes tau pathology?Andreasson et al., 2007.

1. Involvement of the monoaminergic system in pathogenesis of Alzheimer’s disease

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

• Controversial results of the studies on CSF monoamine metabolites in AD patients

Decreased in CSF Increased in CSF Unchanged in CSFhomovanilic acid Kawakatsu et al., 1990

Martignoni et al., 1991 Blennow et al., 1992 Parnetti et al., 1992Sjogren et al., 1998

Zubenko et al., 1986van der Cammen et al., 2006

Sheline et al., 1998Stuerenburg et al., 2004 Parnetti et al., 1992

5-hydroxyindoleacetic acid (5HIAA)

dihydroxyphenylacetic acidmonoamine synthesis cofactor biopterinserotonin Volicer et al., 1985

5-hydroxytryptophan

noradrenaline Sjogren et al., 1998 Toghi et al., 1992 Blennow et al., 1992

3-methoxy-4-hydroxyphenylglycol

Core CSF biomarkers

P-tau181Aβ1-42

T-tau

P-tau199 P-tau231 VILIP-1

Novel CSF biomarkers

Measurement od event-related potentials.

Noninvasively measured potential AD biomarkers

Laczo et al., 2009.

• 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