Multifaceted assessment of the APP/PS1 mouse model for Alzheimer's disease: Applying MRS, DTI, and ASL

Abstract

Transgenic animal models of Alzheimer's disease (AD) can mimic pathological and behavioral changes occurring in AD patients, and are usually viewed as the first choice for testing novel therapeutics. Validated biomarkers, particularly non-invasive ones, are urgently needed for AD diagnosis or evaluation of treatment results. However, there are few studies that systematically characterize pathological changes in AD animal models. Here, we investigated the brain of 8-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic and wild-type (WT) mice, employing 7.0-T magnetic resonance imaging (MRI). Magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) were obtained through micro-MRI scanning. After MRI examination in both transgenic (n = 12) and WT (n = 12) mice, immunohistochemical staining and ultrastructural analysis were subsequently performed. Cerebral blood flow (CBF) was significantly decreased in the left hippocampus, left thalamus, and right cortex of AD mice (P < 0.05). Moreover, MRS showed significantly changed NAA/Cr, Glu/Cr, and mI/Cr ratios in the hippocampus of transgenic mice. While only NAA/Cr and mI/Cr ratios varied significantly in the cortex of transgenic mice. Regarding DTI imaging, however, the values of FA, MD, DA and DR were not significantly different between transgenic and WT mice. Finally, it is worth noting that pathological damage of metabolism, CBF, and white matter was more distinct between transgenic and WT mice by pathological examination. Altogether, our results suggest that intravital imaging evaluation of 8-month-old APP/PS1 transgenic mice by MRS and ASL is an alternative tool for AD research.

Keywords: APP/PS1 transgenic mice; ASL; Alzheimer’s disease; DTI; MRI; MRS.