Citation

Edlow BL, Keene CD, Perl D, Iacono D, Folkerth R, Stewart W, Macdonald CL, Augustinack J, Diaz-Arrastia R, Estrada C, Flannery E, Gordon W, Grabowski T, Hansen K, Hoffman J, Kroenke C, Larson E, Lee P, Mareyam A, McNab JA, McPhee J, Moreau AL, Renz A, Richmire K, Stevens A, Tang CY, Tirrell LS, Trittschuh E, van der Kouwe A, Varjabedian A, Wald LL, Wu O, Yendiki A, Young L, Zollei L, Fischl B, Crane PK, Dams-O'connor K. J. Neurotrauma 2018; 35(14): 1604-1619.

Affiliation

Icahn School of Medicine at Mount Sinai, 5925, Rehabilitation Medicine, New York, New York, United States ; kristen.dams-o'connor@mountsinai.org.

Copyright

(Copyright © 2018, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2017.5457

PMID

29421973

Abstract

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's and Parkinson's disease (AD and PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional MRI, and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

Language: en

Keywords

Behavior; MRI; NEURODEGENERATIVE DISORDERS; TRAUMATIC BRAIN INJURY