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

Area of Science:

• Neuroscience
• Biomedical Imaging
• Genetics

Background:

• Alzheimer's disease (AD) research relies on animal models.
• Transgenic (Tg) mice overexpressing mutated human genes are crucial for modeling AD pathology.
• Comparing different Tg mouse models is essential for identifying reliable biomarkers.

Purpose of the Study:

• To systematically compare double (TASTPM) and triple (APP/PS2/Tau) Tg mice models of Alzheimer's disease.
• To identify homologous biomarkers between mouse models and human AD patients using serial MRI and spectroscopy.
• To evaluate the translational potential of MRI as a preclinical research tool.

Main Methods:

• Serial magnetic resonance imaging (MRI) and spectroscopy were performed on TASTPM and APP/PS2/Tau Tg mice from 4 to 26 months of age.
• Wild-type (WT) mice served as controls.
• Analysis focused on brain structure (hippocampal atrophy, entorhinal cortex thinning, striatal atrophy) and neurochemical changes (glutamate, myo-inositol).

Main Results:

• Both Tg mouse models exhibited hippocampal atrophy compared to WT mice.
• APP/PS2/Tau mice showed age-dependent atrophy, while TASTPM mice displayed it from the earliest time point.
• Common findings included age-related entorhinal cortex thinning, striatal atrophy, and synaptophysin loss. Lower glutamate and increased myo-inositol were observed in specific Tg models.
• MRI revealed homologous biomarkers between Tg mice and human AD patients.

Conclusions:

• Noninvasive MRI analysis identified common biomarkers for Alzheimer's disease in Tg mice and humans.
• The study highlights the translational potential of MRI for preclinical investigations of AD therapeutics.
• TASTPM and APP/PS2/Tau Tg mice offer valuable models for studying AD pathogenesis and evaluating treatments.