Preclinical Neuroimaging in Aging and Alzheimer’s Disease
Our laboratory also conducts research to gain understanding on the link between neuroinflammation, amyloid deposition and neurodegenerative changes involved in Alzheimer’s disease and related dementia’s. Because of the unique anatomical and physiological features of the mammalian brain, we obtain our experimental measurements using functional magnetic resonance imaging (fMRI) at high magnetic field strengths. The method provides a non-invasive means of probing neuronal activity many regions and over the course of disease progression. Indeed, fMRI is a powerful translatable tool that links human studies and animal research directly. In addition to functional changes, we are also interested in exploiting the full capabilities of MRI to assess structural white matter changes with diffusion MRI and other anatomical imaging modalities.
In vivo structural abnormalities and increased free water in mice showing increased Ab42 accumulation: Abnormal b-amyloid (Ab) accumulation is implicated in Alzheimer’s disease (AD) pathogenesis and may partly underlie structural and diffusion abnormalities detected using MRI. However, a direct relationship between Ab accumulation, particularly the toxic Ab42 fragment, and imaging-based pathologies remains difficult to establish. Imaging mutant mouse strains bred to selectively overproduce toxic Ab (Bri2- Ab42 mouse) could offer important insight in this regard. We recently assessed multiple structural features of Bri2-Ab42 mice and age and sex matched wildtype (wt) controls. To assess in vivo interactions between Ab42 overproduction and neuroinflammation, diffusion images were processed for free water (FW) signal. Diffusion images, fluid attenuation inversion recovery (FLAIR) and T2 weighted images were collected at 11.1 Tesla. Our present preliminary results provide evidence that Ab42 production results in structural abnormalities such as enlarged ventricles with surrounding hyperintensities. In addition, a potential link to neuroinflammation is supported by greater FW in Bri2-Aβ42 than in wt mice. In addition to translating results in animal models of toxic Aβ42 to understand mechanisms underlying MRI findings in AD subjects, these biomarkers are expected to offer a powerful approach for determine in vivo therapeutic efficacy.