title: Striatum and entorhinal cortex atrophy in AD mouse models: MRI comprehensive analysis.
abstract: Alzheimer's disease is experimentally modeled in transgenic (Tg) mice overexpressing mutated forms of the human amyloid precursor protein either alone or combined with mutated presenilins and tau. In the present study, we developed a systematic approach to compare double (TASTPM) and triple (APP/PS2/Tau) Tg mice by serial magnetic resonance imaging and spectroscopy analysis from 4 to 26 months of age to define homologous biomarkers between mice and humans. Hippocampal atrophy was found in Tg mice compared with WT. In APP/PS2/Tau the effect was age-dependent, whereas in TASTPM it was detectable from the first investigated time point. Importantly, both mice displayed an age-related entorhinal cortex thinning and robust striatal atrophy, the latter associated with a significant loss of synaptophysin. Hippocampal magnetic resonance spectroscopy revealed lower glutamate levels in both Tg mice and a selective myo-inositol increase in TASTPM. This noninvasive magnetic resonance imaging analysis, revealed common biomarkers between humans and mice, and could, thus, be promoted as a fully translational tool to be adopted in the preclinical investigation of therapeutic approaches.
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Micotti
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Paladini
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Balducci
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tolomeo
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Angelisa
authors.initials: A
authors.lastname: Frasca
authors.affiliation: Laboratory of Epidemiology and Neuroimaging, IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Marizzoni
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Filibian
authors.affiliation: Biomedical Engineering Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Bergamo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caroli
authors.affiliation: MRI Department, Ephoran Multi-Imaging Solutions S.r.l., Colleretto Giacosa Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Valbusa
authors.affiliation: Eli Lilly, Lilly Research Centre, Windlesham, Surrey, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dix
authors.affiliation: Eli Lilly, Lilly Research Centre, Windlesham, Surrey, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: O'Neill
authors.affiliation: CNS Research, Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ozmen
authors.affiliation: CNS Research, Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Czech
authors.affiliation: Neurosciences Therapeutic Area Unit, GlaxoSmithKline R&D, Stevenage, Herts, UK.
authors.forename: Jill C
authors.initials: JC
authors.lastname: Richardson
authors.affiliation: Laboratory of Epidemiology and Neuroimaging, IRCCS Fatebenefratelli, Brescia, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: Neuroscience Department, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy. Electronic address: forloni@marionegri.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001284:Atrophy; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D053763:Presenilins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D005971:Glutamates; D053763:Presenilins; D016875:tau Proteins
keywords: Alzheimer's disease; Animal models; IMI-PharmaCog; MRI; MRS; Pharmacology; Translational research