Histologic lesion type correlates of magnetic resonance imaging biomarkers in four-repeat tauopathies

作者：Arenn F. Carlos, Nirubol Tosakulwong, Stephen D. Weigand, Marina Buciuc, Farwa Ali, Heather M. Clark, Hugo Botha, Rene L. Utianski, Mary M. Machulda, Christopher G. Schwarz, Robert I. Reid, Matthew L. Senjem, Clifford R. Jack, J. Eric Ahlskog, Dennis W. Dickson, Keith A. Josephs, Jennifer L. Whitwell · 发表于：Brain Communications · 年份：2022 · DOI：10.1093/braincomms/fcac108 · 被引用次数：14 · 研究领域：Advanced Neuroimaging Techniques and Applications、Parkinson's Disease Mechanisms and Treatments、Alzheimer's disease research and treatments

Abstract Primary four-repeat tauopathies are characterized by depositions of the four-repeat isoform of the microtubule binding protein, tau. The two most common sporadic four-repeat tauopathies are progressive supranuclear palsy and corticobasal degeneration. Because tau PET tracers exhibit poor binding affinity to four-repeat pathology, determining how well in vivo MRI findings relate to underlying pathology is critical to evaluating their utility as surrogate markers to aid in diagnosis and as outcome measures for clinical trials. We studied the relationship of cross-sectional imaging findings, such as MRI volume loss and diffusion tensor imaging white matter tract abnormalities, to tau histopathology in four-repeat tauopathies. Forty-seven patients with antemortem 3 T MRI volumetric and diffusion tensor imaging scans plus post-mortem pathological diagnosis of a four-repeat tauopathy (28 progressive supranuclear palsy; 19 corticobasal degeneration) were included in the study. Tau lesion types (pretangles/neurofibrillary tangles, neuropil threads, coiled bodies, astrocytic lesions) were semiquantitatively graded in disease-specific cortical, subcortical and brainstem regions. Antemortem regional volumes, fractional anisotropy and mean diffusivity were modelled using linear regression with post-mortem tau lesion scores considered separately, based on cellular type (neuronal versus glial), or summed (total tau). Results showed that greater total tau burden was associated with...