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J Neurol Neurosurg Psychiatry. 2013 Sep;84(9):949-55. doi: 10.1136/jnnp-2012-304418. Epub 2013 Mar 9.

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

Author information

1
Department of Neurology, Perelman School of Medicine, Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. mcmillac@mail.med.upenn.edu

Abstract

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.

KEYWORDS:

Brain Mapping; Dementia; Neuropathology

Comment in

PMID:
23475817
PMCID:
PMC3737288
DOI:
10.1136/jnnp-2012-304418
[Indexed for MEDLINE]
Free PMC Article

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