Victor Villemagne

GRAPHICAL NETWORK ANALYSES INFORMS PET Aβ-AMYLOID BIOMARKER DISCOVERY VIA QUANTIFICATION OF INDIVIDUAL PEPTIDE CONNECTIONS

Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle (ICM), Institut de la M emoire et de la Maladie d’Alzheimer (IM2A), Paris, France; University of Pisa, Pisa, Italy; University of Rome Tor Vergata, Rome, Italy; Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA; Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; AXA Research Fund & UPMC Chair, Paris, France; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, M€olndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M€olndal, Sweden; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; University College London, London, United Kingdom; Laboratoire de Biochimie, AP-HP, Hôpital de la Piti e-Salpêtri ere, Paris, France; Service de Biochimie M etabolique, Hôpital Piti e-Salpêtri ere, Paris, France; Sorbonne Universit es, UPMC Univ Paris 06, CNRS, INSERM, Laboratoire d’Imagerie Biom edicale, F-75013, Paris, France; Sorbonne Universit es, Universit e Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle (ICM), Institut de la M emoire et de la Maladie d’Alzheimer (IM2A), Paris, France; AXA Research Fund & UPMC Chair, Sorbonne Universit es, Universit e Pierre etMarie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle (ICM), Institut de la M emoire et de la Maladie d’Alzheimer (IM2A), Paris, France. Contact e-mail: filippo.baldacci@unipi.it

SELF-REPORTED PHYSICAL ACTIVITY IS ASSOCIATED WITH TAU BURDEN AS MEASURED BY PET

groups were subjected to Ph&M, SI&PM or both of them. Swimming and forced swimming tests were performed each for one time/week during the 4 or 5 weeks of the experiment for maintaining Ph&M. Histopathological changes in different brain regions as well as biochemical changes in Ab, Tau, b-secretase, ACHE, monoamins (DA, NE, 5-HT), inflammatory mediators (TNF-a, IL-1b), oxidative parameters (MDA, SOD, TAC), brain derived neurotrophic factor (BDNF) and DNA fragmentation were measured for all groups.Results:Brain neurological damage characterizing AD or PM associated with SI was more pronounced when AD is associated with PM&SI in rats and the severity increased by time. By maintaining Ph&M; Ab, b-secretase,Tau, ACHE, MDA, TNF-a, IL-1b and DNA fragmentation were significantly decreased while SOD, TAC, DA, NE, 5-HT and BDNF were increased. The protective effect of Ph&M against brain neuronal damage was clearer by time especially when AD is associated with PM&SI. These results were confirmed by the histopathological examinations. Conclusions: Maintaining Ph&M can protect from brain neuronal degenerations induced by AD especially when associated with the risk of PM&SI. The protection was more marked in AD associated risk factors especially during the disease progression.