Ozmen Laurence

CHANGES IN FRONTOCORTICAL INTERSTITIAL FLUID LEVELS OF BETA-AMYLOID AND TAU PROTEIN IN TRANSGENIC MICE MODELS OF ALZHEIMER'S DISEASE

WEDNESDAY, JULY 16, 2014 POSTER PRESENTATIONS P4 P4-001 CHANGES IN FRONTOCORTICAL INTERSTITIAL FLUID LEVELS OF BETA-AMYLOID AND TAU PROTEIN IN TRANSGENIC MICE MODELS OF ALZHEIMER’S DISEASE Alain Gobert, Gaelle Rollin-Jego, Fabrice Iop, Jean Michel Rivet, Dominique Favale, Laurence Danober, Sophie Dix, Christian Czech, Ozmen Laurence, Jill Richardson, Esther Schenker, Institut de Recherches Servier, Croissy sur Seine, France; Institut de Recherches Servier, Croissy sur Seine, France; Institut de Recherches Servier, Croissy sur Seine, France; Eli Lilly, Lilly Research Centre, Surrey, United Kingdom; CNS Research, Hoffmann-La Roche AG, Basel, Switzerland; F. Hoffmann-LaRoche AG, Basel, Switzerland; GlaxoSmithKline Research and Development, China Group, Stevenage, United Kingdom; Institut de Recherches Servier, Croissy sur Seine, France. Contact e-mail: alain.gobert@fr.netgrs.com

MAGNETIC RESONANCE IMAGING AND ALZHEIMER'S DISEASE: A LONGITUDINAL STUDY OF STRUCTURAL CHANGES IN DIFFERENT TRANSGENIC MODELS

Alessandra Paladini, Edoardo Micotti, Angelisa Frasca, Daniele Tolomeo, Moira Marizzoni, Anna Caroli, Claudia Balducci, Sophie Dix, Michael O’Neill, Ozmen Laurence, Christian Czech, Jill Richardson, Giovanni B. Frisoni, Gianluigi Forloni, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; 3 IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; 4 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Eli Lilly, Lilly Research Centre, Surrey, United Kingdom; Eli Lilly, Lilly Research Centre, Windlesham, United Kingdom; 7 CNS Research, Hoffmann-La Roche AG, Basel, Switzerland; 8 GlaxoSmithKline, Stevenage, United Kingdom; 9 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy. Contact e-mail: forloni@ marionegri.it

Characterization of cortical electroencephalographic (EEG) rhythms in three transgenic mouse strains that develop Alzheimer's disease-associated neuropathological features

CA1 unbiased stereology was performed. Spatial reference memory was evaluated using the Morris water maze. In addition, in vitro toxicity of Ab4-42 was studied in primary neurons using a calcein assay. Results: Ab4-42 is a highly toxic peptide as soluble oligomers triggered neuron death in primary cortical neurons. Tg4-42 brain sections showed abundant intraneuronal Ab immunoreactivity predominantly in the CA1 pyramidal cell layer of the hippocampus beginning at the age of two months. Aß4-42 could also be detected in the occipital cortex, piriform cortex, striatum and superior colliculus. In addition, increased astrogliosis and microgliosis was observed at two months of age. Eight months old homozygous Tg4-42 mice showed severe neuron loss (66%) in CA1 region accompanied by impaired spatial reference memory accessed in the Morris water maze. Neuron number in different brain regions will be investigated and presented. Conclusions: The Tg4-42 model represents the first mouse model expressing exclusively N-truncated Aß4-42. Long-term exposure to soluble Aß4-42 oligomers induces severe hippocampal neuron loss and age-dependent deficits in spatial reference memory that are compatible with AD-typical changes.

1H magnetic resonance spectroscopy longitudinal study in different transgenic mouse models of Alzheimer's disease

P1-132 1H MAGNETIC RESONANCE SPECTROSCOPY LONGITUDINAL STUDY IN DIFFERENT TRANSGENIC MOUSE MODELS OF ALZHEIMER’S DISEASE Alessandra Paladini, Marta Filibian, Edoardo Micotti, Claudia Balducci, Sophie Dix, Michael O’Neill, Ozmen Laurence, Christian Czech, Jill Richardson, Gianluigi Forloni, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; Istituto di Ricerche Farmacologiche Mario Negri, Department of Physics ‘A. Volta,’ University of Pavia, Milano/Pavia, Italy; 3 Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy; Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; Eli Lilly, Lilly Research Centre, Surrey, United Kingdom; 6 CNS Research, Hoffmann-La Roche AG, Basel, Switzerland; 7 GlaxoSmithKline, Stevenage, United Kingdom.