Increased Neurite Orientation-Dispersion and Density in the TgCRND8 Mouse Model of Amyloidosis: Inverse Relation with Functional Connectome Clustering and Modulation by Interleukin-6

Luis M. Colon-Perez; Kristen R. Ibanez; Mallory Suarez; Kristin Torroella; Kelly Acuna; Edward Ofori; Yona Levites; David E. Vaillancourt; Todd E. Golde; Paramita Chakrabarty; Marcelo Febo

Diffusion tensor imaging (DTI) offers a powerful approach to generate metrics that describe the movement of water in brain tissue compartments. Advanced methods for the modeling of tissue diffusivity beyond standard DTI processing schemes may provide additional insight on the effects of pathogenic Aβ and immune mechanisms in Alzheimer's disease. For example, increased radial diffusivity was associated with worsening of dementia symptoms in dMRI scans processed using a two-compartment model of diffusion known as the free water imaging method (Ji et al., 2017; Maier-Hein et al., 2015) . Also, a multi-compartment diffusion model termed 'Neurite Orientation Dispersion and Density Imaging' (NODDI) revealed significant changes in NODDI metrics in young onset Alzheimer's disease (Parker et al., 2018; Slattery et al., 2017) , and correlations with cortical tau immunoreactivity in the rTg4510 mouse tauopathy model of frontal temporal dementia (Colgan et al., 2016) . The free water method (Pasternak et al., 2009) provides quantitative maps that have been associated with neuroinflammatory and neurodegenerative mechanisms (Ofori et al., 2015; Pasternak et al., 2012; Pasternak et al., 2015) , and the NODDI model provides quantitative maps associated with axonal and dendritic dispersion and density (Colgan et al., 2016; Grussu et al., 2017; Zhang et al., 2012) . Despite the advances in dMRI processing, preclinical high field imaging studies in mouse models are needed to determine the changes in brain microstructure that link to Aβ or neuroinflammation, and the impact of such changes on functional network activity.