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

TgCRND8 mice were maintained in-house by breeding amyloid precursor protein (APP) transgenic (Tg) males (carrying the wild-type retinal degeneration gene) with C57B6/C3H F1 females (Envigo) (Janus et al., 2000) . TgCRND8 mice have early onset expression of human mutant APP (Swedish APP KM670/671NL and Indiana APP V717F), which increases human APP 5-times above endogenous murine APP. These mice have aggressive cognitive impairment, Aβ plaque deposits and increased inflammation at 3-4 months of age, synaptic deficits and some synaptic and neuronal loss in hippocampus by 6 mo. (Chishti et al., 2001) . In this study, we used 8 month old mice (non-transgenic (nTg) and TgCRND8), an age where there is high levels of forebrain amyloidosis. All groups were sex and age-matched. All procedures received prior approval from the Institutional Animal Care and Use Committee of the University of Florida and follow all applicable NIH guidelines.