Citation

Kenney K, Iacono D, Edlow BL, Katz DI, Diaz-Arrastia R, Dams-O'connor K, Daneshvar DH, Stevens A, Moreau AL, Tirrell LS, Varjabedian A, Yendiki A, van der Kouwe A, Mareyam A, McNab JA, Gordon WA, Fischl B, McKee AC, Perl DP. J. Neuropathol. Exp. Neurol. 2018; 77(1): 50-63.

Affiliation

Department of Neurology; Department of Pathology, F. Edward Hébert School of Medicine; Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University of the Health Sciences (USUHS), Bethesda, Maryland; The Henry M. Jackson Foundation for the Advancement of Military Research (HJF); Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Boston Massachusetts; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts; Department of Neurology; Alzheimer's Disease Center and CTE Program, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Rehabilitation Medicine; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York; Radiological Sciences Laboratory, Department of Radiology, Stanford University, Stanford, California; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Boston, Massachusetts; VA Boston Healthcare System, Boston, Massachusetts; and Department of Pathology, Boston University School of Medicine, Boston, Massachusetts.

Copyright

(Copyright © 2018, American Association of Neuropathologists, Publisher Lippincott Williams and Wilkins)

DOI

10.1093/jnen/nlx101

PMID

29155947

Abstract

We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.

2017 American Association of Neuropathologists, Inc. This work is written by US Government employees and is in the public domain in the US.

Language: en

Keywords

Hyperphosphorylated tau; Neurodegeneration; Neurofibrillary tangle; Proteinopathy; Traumatic brain injury; α-Synuclein; β-Amyloid