TY - JOUR
T1 - Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer's disease
AU - Wang, Qing
AU - Wang, Yong
AU - Liu, Jingxia
AU - Sutphen, Courtney L.
AU - Cruchaga, Carlos
AU - Blazey, Tyler
AU - Gordon, Brian A.
AU - Su, Yi
AU - Chen, Charlie
AU - Shimony, Joshua S.
AU - Ances, Beau M.
AU - Cairns, Nigel J.
AU - Fagan, Anne M.
AU - Morris, John C.
AU - Benzinger, Tammie L.S.
N1 - Funding Information:
The authors thank all of the research volunteers for their contributions. The authors thank Dr. Sheng-Kwei Song, PhD, for his advice and Dr. Deborah J. Frank, PhD, for her help in editing the manuscript. This study was supported, in part, by grants from the National Institutes of Health (NIH) including the National Institutes on Aging (NIA) P01AG026276 ( Antecedent Biomarkers of AD : the Adult Children Study, PI J. C. Morris); NIA P01AG003991 ( Healthy Aging and Senile Dementia , PI J. C. Morris); NIA P50AG05681 ( Alzheimer's disease Research Center , PI J. C. Morris); NIA 1R01AG054567-01A1(PIs T.L.S. Benzinger and Y. Wang,) and Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences. This work used the services of the imaging facility informatics platform, supported by NIH grant 5P30NS048056 (PI D. S. Marcus). This work was also funded by a grant from the National Multiple Sclerosis Society RG5265 A1 (PI Y. Wang). Additional support was generously provided by the Charles and Joanne Knight Alzheimer's Research Initiative and by the Fred Simmons and Olga Mohan Fund and the Paula and Rodger Riney Fund . Support was also provided by NIH U54 HD087011 the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health to the Intellectual and Developmental Disabilities Research Center at Washington University (PI J.S. Shimony).
Funding Information:
The authors thank all of the research volunteers for their contributions. The authors thank Dr. Sheng-Kwei Song, PhD, for his advice and Dr. Deborah J. Frank, PhD, for her help in editing the manuscript. This study was supported, in part, by grants from the National Institutes of Health (NIH) including the National Institutes on Aging (NIA) P01AG026276 (Antecedent Biomarkers of AD: the Adult Children Study, PI J. C. Morris); NIA P01AG003991 (Healthy Aging and Senile Dementia, PI J. C. Morris); NIA P50AG05681 (Alzheimer's disease Research Center, PI J. C. Morris); NIA 1R01AG054567-01A1(PIs T.L.S. Benzinger and Y. Wang,) and Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences. This work used the services of the imaging facility informatics platform, supported by NIH grant 5P30NS048056 (PI D. S. Marcus). This work was also funded by a grant from the National Multiple Sclerosis Society RG5265 A1 (PI Y. Wang). Additional support was generously provided by the Charles and Joanne Knight Alzheimer's Research Initiative and by the Fred Simmons and Olga Mohan Fund and the Paula and Rodger Riney Fund. Support was also provided by NIH U54 HD087011 the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health to the Intellectual and Developmental Disabilities Research Center at Washington University (PI J.S. Shimony). Q.W. Y.W. T.L.S.B. J.S.S. B.M.A. Y. S. N.J.C. A.M.F. and J.C.M. designed the research; Q.W. Y.W. T.L.S.B. J.S.S. T.B. B.A.G. Y.S. C.L.S, E.M.H. N.J.C. A.M.F. and J.C.M. performed the research. Q.W. Y.W. T.B. Y.S. J.L. C.L.S, E.M.H. analyzed data, and Q.W. Y.W. T.L.S.B. B.A.G. Y.S. B.M.A. A.M.F. and J.C.M. wrote the paper.
Publisher Copyright:
© 2019 The Authors
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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 Aβ 42 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.
AB - 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 Aβ 42 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.
KW - Cerebrospinal fluid
KW - Diffusion basis spectrum imaging
KW - Early symptomatic Alzheimer disease
KW - Inflammation
KW - Magnetic resonance imaging
KW - Neuro-inflammation imaging
KW - Preclinical Alzheimer disease
KW - White matter damage
UR - http://www.scopus.com/inward/record.url?scp=85063053657&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2019.101767
DO - 10.1016/j.nicl.2019.101767
M3 - Article
C2 - 30901713
AN - SCOPUS:85063053657
VL - 22
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
SN - 2213-1582
M1 - 101767
ER -