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

Also recently, Brown and colleagues observed that decreased default mode network (DMN) deactivation during a working memory task was associated with Alzheimer's disease pathology and cognitive decline (Brown et al., 2018) . Interestingly, decline in WM integrity was reported to influence the reduced DMN deactivation, suggesting a relationship between microstructural differences between controls and Alzheimer's disease subjects and network activity. Our results suggest a negative relationship potentially involving reduced activity or reduced modular organization in Alzheimer's disease mice and with IL6 treatment, which is contrary to the positive relationship reported by Ocklenberg et al (Ocklenburg et al., 2018) and Brown et al (Brown et al., 2018) . A possibility is that the increased NDI and ODI in the present work, and its association with reduced clustering, might involve increased presence of neuroglial cells (as noted above) and not necessarily changes in the density of functionally active axons and dendritic processes. Moreover, the fact that both NDI and ODI were increased may suggest atrophic microstructural changes in TgCRND8 and IL6 treated mice that may adversely impact neural processing. It will be interesting to resolve such interactions between these two different imaging modalities. The relationship between NODDI and graph theory metrics warrants further investigation in the development of novel biomarkers for Alzheimer's disease and other neurodegenerative diseases. All rights reserved. No reuse allowed without permission.