Format

Send to

Choose Destination
Neuroimage. 2019 Nov 15;202:116138. doi: 10.1016/j.neuroimage.2019.116138. Epub 2019 Aug 28.

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

Author information

1
Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, United States; Department of Psychiatry, University of Florida, Gainesville, United States.
2
Center for Translational Research on Neurodegenerative Diseases, University of Florida, Gainesville, United States; Department of Neuroscience, University of Florida, Gainesville, United States.
3
Department of Psychiatry, University of Florida, Gainesville, United States.
4
Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, United States; Applied Physiology & Kinesiology, University of Florida, Gainesville, United States.
5
Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, United States; Center for Translational Research on Neurodegenerative Diseases, University of Florida, Gainesville, United States; Department of Neuroscience, University of Florida, Gainesville, United States; McKnight Brain Institute, University of Florida, Gainesville, United States.
6
Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, United States; Advanced Magnetic Resonance Imaging and Spectroscopy Facility, University of Florida, Gainesville, United States; Department of Psychiatry, University of Florida, Gainesville, United States; Applied Physiology & Kinesiology, University of Florida, Gainesville, United States.
7
Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, United States; Center for Translational Research on Neurodegenerative Diseases, University of Florida, Gainesville, United States; Department of Neuroscience, University of Florida, Gainesville, United States; McKnight Brain Institute, University of Florida, Gainesville, United States. Electronic address: pchakrabarty@ufl.edu.
8
Florida Alzheimer's Disease Research Center, University of Florida, Gainesville, United States; Advanced Magnetic Resonance Imaging and Spectroscopy Facility, University of Florida, Gainesville, United States; Department of Psychiatry, University of Florida, Gainesville, United States; McKnight Brain Institute, University of Florida, Gainesville, United States. Electronic address: febo@ufl.edu.

Abstract

Extracellular β-amyloid (Aβ) 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 Aβ and inflammatory interleukin-6 (IL6), alone or in combination, on in vivo tissue microstructure in the TgCRND8 mouse model of Alzheimer's-type Aβ 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 Aβ 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.

KEYWORDS:

Alzheimer’s disease; Clustering; Connectomic; DTI; Diffusion MRI; Free water; Functional connectivity; Inflammation; Interleukin 6; NODDI

PMID:
31472250
PMCID:
PMC6894485
[Available on 2020-11-15]
DOI:
10.1016/j.neuroimage.2019.116138

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center