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

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?

How are monoaminergic nuclei involved in this process?

1) Šimić et al., 2014.

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.

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 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

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

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.

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