Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis

被引:30
作者
Colon-Perez, Luis M. [1 ,4 ]
Ibanez, Kristen R. [2 ,5 ]
Suarez, Mallory [4 ]
Torroella, Kristin [4 ]
Acuna, Kelly [1 ,6 ]
Ofori, Edward [1 ,2 ,5 ,7 ]
Levites, Yona [1 ,3 ,4 ,6 ]
Vaillancourt, David E. [1 ,2 ,5 ,7 ]
Golde, Todd E. [1 ,2 ,5 ,7 ]
Chakrabarty, Paramita [1 ,3 ,4 ,7 ]
Febo, Marcelo [1 ,3 ,4 ,7 ]
机构
[1] Univ Florida, Florida Alzheimers Dis Res Ctr, Gainesville, FL 32610 USA
[2] Univ Florida, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA
[3] Univ Florida, Adv Magnet Resonance Imaging & Spect Facil, Gainesville, FL 32610 USA
[4] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA
[5] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA
[6] Univ Florida, Appl Physiol & Kinesiol, Gainesville, FL 32610 USA
[7] Univ Florida, McKnight Brain Inst, Gainesville, FL 32610 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
Alzheimer's disease; Diffusion MRI; Functional connectivity; Connectomic; Clustering; NODDI; Free water; DTI; Inflammation; Interleukin; 6; IN-VIVO DETECTION; ALZHEIMERS-DISEASE; TRANSGENIC MICE; MICROGLIAL ACTIVATION; DIFFUSION MRI; FUNCTIONAL CONNECTIVITY; BRAIN-INJURY; FREE-WATER; BETA; DEGENERATION;
D O I
10.1016/j.neuroimage.2019.116138
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Extracellular beta-amyloid (A beta) plaque deposits and inflammatory immune activation are thought to alter various aspects of tissue microstructure, such as extracellular free water, fractional anisotropy and diffusivity, as well as the density and geometric arrangement of axonal processes. Quantifying these microstructural changes in Alzheimer's disease and related neurodegenerative dementias could serve to monitor or predict disease course. In the present study we used high-field diffusion magnetic resonance imaging (dMRI) to investigate the effects of A beta and inflammatory interleukin-6 (IL6), alone or in combination, on in vivo tissue microstructure in the TgCRND8 mouse model of Alzheimer's-type A beta deposition. TgCRND8 and non-transgenic (nTg) mice expressing brain-targeted IL6 or enhanced glial fibrillary protein (EGFP controls) were scanned at 8 months of age using a 2-shell, 54-gradient direction dMRI sequence at 11.1 T. Images were processed using the diffusion tensor imaging (DTI) model or the neurite orientation dispersion and density imaging (NODDI) model. DTI and NODDI processing in TgCRND8 mice revealed a microstructure pattern in white matter (WM) and hippocampus consistent with radial and longitudinal diffusivity deficits along with an increase in density and geometric complexity of axonal and dendritic processes. This included reduced FA, mean, axial and radial diffusivity, and increased orientation dispersion (ODI) and intracellular volume fraction (ICVF) measured in WM and hippocampus. IL6 produced a 'protective-like' effect on WM FA in TgCRND8 mice, observed as an increased FA that counteracted a reduction in FA observed with endogenous A beta production and accumulation. In addition, we found that ICVF and ODI had an inverse relationship with the functional connectome clustering coefficient. The relationship between NODDI and graph theory metrics suggests that currently unknown microstructure alterations in WM and hippocampus are associated with diminished functional network organization in the brain.
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页数:16
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