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

As indicated in the introduction, Aβ and neuroinflammatory mechanisms overlap in the Alzheimer's disease brain and their corresponding roles in pathological progression of dementia warrants investigation. Six-month old 5xFAD mice showed significant brain accumulation of activated microglia-specific protein tracer TSPO (Mirzaei et al., 2016) . In PS2APP mice, there are significant increases in both Aβ and microglia levels from 5month to 16 months of age (Brendel et al., 2016) . This is partially consistent with results in humans showing that in advanced Alzheimer's disease there is a close relationship between amyloid burden with neuroinflammation (Kreisl et al., 2013) . However, non-Alzheimer's disease individuals with mild cognitive impairment (MCI) either fail to show significant microgliosis concomitant with regions of high amyloid burden (Kreisl et al., 2013) , or only a subset of MCI subjects show overlapping increases in amyloid and neuroinflammation (Parbo et al., 2017) . A longitudinal study identified a transient elevation in microglia early in MCI which then peaks again later in Alzheimer's disease (Fan et al., 2017) .