Biomarkers in Clinical Neurosciences
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1 Biomarkers in Clinical Neurosciences U. Bonuccelli,G.Siciliano, R.Ceravolo, M.Mancuso, L.Pasquali, G.Tognoni, F.Giorgi, F.Baldacci, D.Frosini, L.Kiferle,E.Bonanni (m.d.) A. Lo Gerfo, L. Chico, L.Petrozzi (biol.) F.Sartucci E.Santarcangelo
2 ALS: CAUSATIVE GENE Genome Wide Association study IDENTIFICATION Malattia neurodegenerativa cronica progressiva che coinvolge selettivamente, in modo variabile o combinato, il motoneurone superiore (corticale) ed il motoneurone inferiore (spinale) Italy a Pis a
3 ALS: PATHOGENIC MECHANISMS Exercise, mitocondria and oxidative stress Oxidative stress At onset disease Genetic suscetibility Plasma carnitines Nrf2 Mass spectroscopy and plasma carnitines
4
5 Parkinson s Disease
6 LINES OF RESEARCH IN NEURODEGENERATIVE DISEASES Associated Genes of susceptibility to disease Molecular signatures of disease High field MRI (3 and 7 Tesla) Imaging Molecular Imaging with new tracers
7 Ongoing research on genetics & epigenetics of AD In collaboration with the Alzheimer s Disease Genetic Consortium (ADGC): PLoS One Jun 12;9(6) Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.escott-price V, Bellenguez C, Wang LS et al. Nat Genet Dec;45(12): Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer s disease.lambert JC, Ibrahim-Verbaas CA, Harold D, et al. In collaboration with Prof. Migliore and Dr.Coppedè: Identification of biomarkers of folate metabolism and their relation with -Genetic biomarkers (gene polimorphisms: MTHFR, RFC-1, MTR, TYMS, DNMT3A, DNMT3B) ) -Epigenetic biomarkers (methylation of genes associated to AD: presenilin1 PSEN1 and beta-secretase BACE1)
8 Core biomarkers in AD measurable in CSF Core biomarkers in PD measurable in CSF Alfa synuclein : Alfa syn.oligomers : CSF CSF Plasma Plasma Skin Salivary Glands DIAGNOSTIC MARKERS MONITORING PROGRESSION
9 2012 A molecular signature in blood identifies early Parkinson s disease Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1 huntingtin interacting protein-2 aldehyde dehydrogenase family 1 subfamily A1 19 S proteasomal protein PSMC4 heat shock 70-kDa protein 8
10 Future perspectives The PDx assay ongoing study is intended to be an affordable blood test that can easily and specifically diagnose early PD with a potential to identify individuals at pre-symptomatic, prodromal stages of the disease The main objective of the study is to to validate the ability of the expression levels of EGLN, HIP2, HSPA8, ALDH1A1, PSMC4, SKP1A to differentiate between PD patients,hc and atypical parkinsonism patients.
11 MR Imaging of the Substantia Nigra at 7 T Enables Diagnosis of Parkinson Disease Cosottini et al.2014
12 Alzheimer s Disease Cells loss atrophy Ultra high field MRI Amyloid plaques Neurofibrillary tangle beyond the detection limit of any current MRI technology
13 NEUROMODULATION, ELECTROPHYSIOLOGY AND BRAIN DISORDERS Department of Clinical and Experimental Medicine, Cisanello Neurology Unit, Pisa University Medical School Chair: prof. Ferdinando Sartucci Tommaso Bocci, M.D.; Andrea Di Rollo, M.D.; Elisa Giorli, M.D.; Antonio Torzini, M.D. Davide Barloscio, Michelangelo Bartolotta, Orietta Ricci, Laura Masoni, Michela Santin Corpus Callosum and Visual System: role in contrast gain control, Corpus Callosum and Amblyopia Evidence that a mechanism of transcallosal inhibition dampens neural responses at high contrasts in human visual cortex Evidence that neuromodulation techniques are able to dinamically interfere with visual cortex plasticity in amblyopic patients, by restoring a sub-normal visual acuity. Photosensitive Epilepsy Photosensitivity could be due, at least in part, to a functional impairment of inter-hemispheric processing of gain contrast control Bocci et al., 2011 Neuroscience 187: Bocci et al., 2014 Reviews in the Neuroscience 25(1):
14 Further Research Lines 1) Neuromodulation techniques (rtms, tdcs, tsdcs) and pain treatment (Truini et al., 2009 Eur J Pain 14(2): 222-5) 2) Assessment of Olfactory Function in Neurodegenerative Disorders 3) Discover Visual System Plasticity as revealed by neuromodulation techniques (Bocci et al., 2014 J Neural Transm, 121, ) 4) Visual System and Neurodegenerative Disorders (Sannita et al., 2009 Vision Res 49(7): ; Sartucci et al., 2010 Brain Res Bull 82(3-4): ) 5) Monitoring Amyotrophic Lateral Sclerosis and other Motor Neuron Diseases progression with neurophysiological assessment (MUNE, Macro-EMG) (Sartucci et al., 2010 Neural Reg Res 5(8), ; Sartucci et al., 2011 Intern J Neurosci, 121 (5)257-66; Bocci et al., 2011 Int J Mol Sci, 12, ; Bocci et al., 2012 JNS :67-71; Bocci & Sartucci, 2012, J Neurol Neurophysiol 3 (3): e109) 6) Brain mechanisms of Spinal-induced plasticity (Bocci et al, 2014 Neurosci Lett S (14) ) 7) EEG-fMRI recordings in Epilepsies (Cosottini et al., 2010 Magn Reson Imaging, 28(3): ; Pesaresi et al., 2011 MAGMA, 24(5): ; Guida et al., 2014 Funct Neurol, 75-79; Bartolini et al., 2014 EPI, 1-10) 8) Computer-brain interfaces (Bocci et al., 2013 Behav Brain Funct, 9(1), 14) For references and further information: f.sartucci@neuro.med.unipi.it
15 Hypnotizability is a cognitive trait enabling individuals to accept suggestions by modifying perception, memory and behavior. It is measured by scales. (American Psychological Association, 2005) Hypnotizability is a physiological trait - characterized by peculiar a) cortical dynamic b) sensori-motor integration c) cardiovascular control d) cognitive strategies in the ordinary state of consciousness and also in the absence of suggestions. (Santarcangelo, 2014)
16 Subjects with high and low hypnotizability scores have different: cortical dynamics (Madeo et al., 2013) internal models for posture and locomotion responsiveness to the alteration of various sensory modalities excitability of the spinal cord motoneurons haptic abilities degree of embodiment of mental images in neural circuits ( Santarcangelo, Front Behav Neurosci 2014) blink rate (under revision) efficiency of the endothelial function (NO availability ) (Jambrik et al., 2004, 2005,2005) heart rate variability in resting conditions (Santarcangelo et al., Int J Clin Exp Hypn 2012) interaction of imagery with other cognitive emotional traits in pain control (Santarcangelo et al., Plos One 2013, Neurosci Lett 2013) written production (Marinelli et al Int J Clin Exp Hypn, 2012) Hypnotizability is not merely a cognitive trait: its assessment is useful in clinical contexts and its related physiological and cognitive characteristics can be useful tools in neuro-rehabilitation therapies and pain control
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