Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer's disease.
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.
['Wang|Qing|Q|', 'Wang|Yong|Y|', 'Liu|Jingxia|J|', 'Sutphen|Courtney L|CL|', 'Cruchaga|Carlos|C|', 'Blazey|Tyler|T|', 'Gordon|Brian A|BA|', 'Su|Yi|Y|', 'Chen|Charlie|C|', 'Shimony|Joshua S|JS|', 'Ances|Beau M|BM|', 'Cairns|Nigel J|NJ|', 'Fagan|Anne M|AM|', 'Morris|John C|JC|', 'Benzinger|Tammie L S|TLS|']
D000368:Aged D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D015415:Biomarkers D038524:Diffusion Magnetic Resonance Imaging D005260:Female D006801:Humans D007091:Image Processing, Computer-Assisted D007249:Inflammation D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D010446:Peptide Fragments D062706:Prodromal Symptoms D066127:White Matter
Inflammation Magnetic resonance imaging Neuro-inflammation imaging Cerebrospinal fluid Diffusion basis spectrum imaging Early symptomatic Alzheimer disease Preclinical Alzheimer disease White matter damage