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White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration

McMillan, Corey T ; Irwin, David J ; Avants, Brian B ; Powers, John ; Cook, Philip A ; Toledo, Jon B ; McCarty Wood, Elisabeth ; Van Deerlin, Vivianna M ; Lee, Virginia M-Y ; Trojanowski, John Q ; Grossman, Murray

Journal of neurology, neurosurgery and psychiatry, 2013-09, Vol.84 (9), p.949-955 [Periódico revisado por pares]

England: BMJ Publishing Group Ltd

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Título:
White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration
Autor: McMillan, Corey T ; Irwin, David J ; Avants, Brian B ; Powers, John ; Cook, Philip A ; Toledo, Jon B ; McCarty Wood, Elisabeth ; Van Deerlin, Vivianna M ; Lee, Virginia M-Y ; Trojanowski, John Q ; Grossman, Murray
Assuntos: Aged ; Alzheimer's disease ; Anisotropy ; Autopsies ; Autopsy ; Brain - pathology ; Brain Mapping ; Cohort Studies ; Corpus Callosum - pathology ; Dementia ; Diagnosis, Differential ; Diffusion Tensor Imaging ; Disease ; DNA-Binding Proteins - metabolism ; Education ; Educational Status ; Female ; Frontotemporal Lobar Degeneration - diagnosis ; Frontotemporal Lobar Degeneration - pathology ; Humans ; Image Processing, Computer-Assisted ; Male ; Medical imaging ; Middle Aged ; Mutation ; Neuroimaging ; Neuropathology ; Neuropsychological Tests ; Pathology ; ROC Curve ; tau Proteins - metabolism ; TDP-43 Proteinopathies - metabolism ; TDP-43 Proteinopathies - pathology
É parte de: Journal of neurology, neurosurgery and psychiatry, 2013-09, Vol.84 (9), p.949-955
Notas: PMID:23475817
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Descrição: Background Frontotemporal lobar degeneration (FTLD) is most commonly associated with TAR-DNA binding protein (TDP-43) or tau pathology at autopsy, but there are no in vivo biomarkers reliably discriminating between sporadic cases. As disease-modifying treatments emerge, it is critical to accurately identify underlying pathology in living patients so that they can be entered into appropriate etiology-directed clinical trials. Patients with tau inclusions (FTLD-TAU) appear to have relatively greater white matter (WM) disease at autopsy than those patients with TDP-43 (FTLD-TDP). In this paper, we investigate the ability of white matter (WM) imaging to help discriminate between FTLD-TAU and FTLD-TDP during life using diffusion tensor imaging (DTI). Methods Patients with autopsy-confirmed disease or a genetic mutation consistent with FTLD-TDP or FTLD-TAU underwent multimodal T1 volumetric MRI and diffusion weighted imaging scans. We quantified cortical thickness in GM and fractional anisotropy (FA) in WM. We performed Eigenanatomy, a statistically robust dimensionality reduction algorithm, and used leave-one-out cross-validation to predict underlying pathology. Neuropathological assessment of GM and WM disease burden was performed in the autopsy-cases to confirm our findings of an ante-mortem GM and WM dissociation in the neuroimaging cohort. Results ROC curve analyses evaluated classification accuracy in individual patients and revealed 96% sensitivity and 100% specificity for WM analyses. FTLD-TAU had significantly more WM degeneration and inclusion severity at autopsy relative to FTLD-TDP. Conclusions These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLD-TAU, and emphasise the role of WM neuroimaging for in vivo discrimination between FTLD-TAU and FTLD-TDP.
Editor: England: BMJ Publishing Group Ltd
Idioma: Inglês

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White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration

McMillan, Corey T ; Irwin, David J ; Avants, Brian B ; Powers, John ; Cook, Philip A ; Toledo, Jon B ; McCarty Wood, Elisabeth ; Van Deerlin, Vivianna M ; Lee, Virginia M-Y ; Trojanowski, John Q ; Grossman, Murray

England: BMJ Publishing Group Ltd

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