Striatum and entorhinal cortex atrophy in AD mouse models: MRI comprehensive analysis

Edoardo Micotti, Alessandra Paladini, Claudia Balducci, Daniele Tolomeo, Angelisa Frasca, Moira Marizzoni, Marta Filibian, Anna Caroli, Giovanni Valbusa, Sophie Dix, Mike O'Neill, Laurence Ozmen, Christian Czech, Jill C. Richardson, Giovanni B. Frisoni, Gianluigi Forloni

Research output: Contribution to journalArticlepeer-review

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 26months 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.

Original languageEnglish
Pages (from-to)776-788
Number of pages13
JournalNeurobiology of Aging
Volume36
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

Keywords

  • Alzheimer's disease
  • Animal models
  • IMI-PharmaCog
  • MRI
  • MRS
  • Pharmacology
  • Translational research

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Medicine(all)

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