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Neuroimage Clin. 2019;22:101767. doi: 10.1016/j.nicl.2019.101767. Epub 2019 Mar 13.

Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer's disease.

Author information

1
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA.
2
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University School of Engineering & Applied Science, St. Louis, MO 63015, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: wangyong@wustl.edu.
3
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
7
Banner Alzheimer's Institute, Phoenix, AZ 85006, USA.
8
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
9
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
10
Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
11
Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
12
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, 4488 Forest Park, Suite 101, St. Louis, MO 63108, USA; Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.

Abstract

Interest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion-based MRI method, neuro-inflammation imaging (NII), has been developed to clinically image and quantify WM inflammation and damage in AD. Here, we employed NII measures in conjunction with cerebrospinal fluid (CSF) biomarker classification (for β-amyloid (Aβ) and neurodegeneration) to evaluate 200 participants in an ongoing study of memory and aging. Elevated NII-derived cellular diffusivity was observed in both preclinical and early symptomatic phases of AD, while disruption of WM integrity, as detected by decreased fractional anisotropy (FA) and increased radial diffusivity (RD), was only observed in the symptomatic phase of AD. This may suggest that WM inflammation occurs earlier than WM damage following abnormal Aβ accumulation in AD. The negative correlation between NII-derived cellular diffusivity and CSF Aβ42 level (a marker of amyloidosis) may indicate that WM inflammation is associated with increasing Aβ burden. NII-derived FA also negatively correlated with CSF t-tau level (a marker of neurodegeneration), suggesting that disruption of WM integrity is associated with increasing neurodegeneration. Our findings demonstrated the capability of NII to simultaneously image and quantify WM cellularity changes and damage in preclinical and early symptomatic AD. NII may serve as a clinically feasible imaging tool to study the individual and composite roles of WM inflammation and damage in AD.

KEYWORDS:

Cerebrospinal fluid; Diffusion basis spectrum imaging; Early symptomatic Alzheimer disease; Inflammation; Magnetic resonance imaging; Neuro-inflammation imaging; Preclinical Alzheimer disease; White matter damage

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