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

We also assessed NODDI metrics (Zhang et al., 2012) in the same animals processed for DTI and free water. The neurite density index (NDI) has been shown to correlate with histological markers of axonal or dendritic processes (Grussu et al., 2017) , and changes in this NODDI metric has been associated with neurodegenerative changes (Colgan et al., 2016; Grussu et al., 2017; Parker et al., 2018) . We observed that Aβ expression in TgCNRD8 mice was associated with increases in both NDI and the orientation dispersion index (ODI) in WM and hippocampus. At first glance this finding may seem counterintuitive considering the above-described reduced microstructural integrity. However, the results are consistent with previously reported negative correlations between FA and ODI (Zhang et al., 2012) . Low FA values in WM correlate with high ODI, and this latter metric can show a positive correlation with NDI (Zhang et al., 2012) . From a physiological standpoint, the co-occurrence of reduced microstructural integrity of axons along with increased density of misoriented axonal/dendritic processes in WM and hippocampus seems plausible given previously reported increases in activated microglial cells along with amyloid plaque-associated structural changes to neurons in mouse models with increased Aβ expression.