Dementia After Moderate-Severe Traumatic Brain Injury: Coexistence of Multiple Proteinopathies

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, an...

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Published inJournal of neuropathology and experimental neurology Vol. 77; no. 1; pp. 50 - 63
Main Authors Kenney, Kimbra, Iacono, Diego, Edlow, Brian L, Katz, Douglas I, Diaz-Arrastia, Ramon, Dams-O'Connor, Kristen, Daneshvar, Daniel H, Stevens, Allison, Moreau, Allison L, Tirrell, Lee S, Varjabedian, Ani, Yendiki, Anastasia, van der Kouwe, Andre, Mareyam, Azma, McNab, Jennifer A, Gordon, Wayne A, Fischl, Bruce, McKee, Ann C, Perl, Daniel P
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.01.2018
Subjects
Adult
Aged
Brain - diagnostic imaging
Brain - metabolism
Brain - pathology
Brain Injuries, Traumatic - complications
Brain Injuries, Traumatic - diagnostic imaging
Brain Injuries, Traumatic - metabolism
Brain Injuries, Traumatic - pathology
Dementia
Dementia - diagnostic imaging
Dementia - etiology
Dementia - metabolism
Dementia - pathology
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Neurofibrillary Tangles - metabolism
Neurofibrillary Tangles - pathology
Neuroimaging
Neuropathology
Original
Plaque, Amyloid - diagnostic imaging
Plaque, Amyloid - metabolism
Plaque, Amyloid - pathology
tau Proteins - metabolism
Traumatic brain injury
α-Synuclein
Proteinopathy
Traumatic brain injury
Neurodegeneration
β-Amyloid
Hyperphosphorylated tau
Neurofibrillary tangle
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Summary: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.
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Supplementary Data can be found at http://www.jnen.oxfordjournals.org.
Supported by Chronic Effects of Neurotrauma Consortium (DoD & VA), Award Number W81XWH-13-2-0095 and VA award IO1RX 002170; The Brain Tissue Repository (BTR) and Neuropathology Core, CNRM, USUHS, CNRM Award Number 308049-4.01-60855; Boston University Alzheimer’s disease Center NIA P30 AG13846, supplement 0572063345-5; Department of Veterans Affairs; Worldwide Wrestling Foundation and the Andlinger Foundation; American Academy of Neurology/American Brain Foundation; the James S. McDonnell Foundation; the National Center for Research Resources (P41RR014075, U24 RR021382); the National Institute for Biomedical Imaging and Bioengineering (P41EB015896, R01EB006758, R21EB018907, R01EB019956, R21EB018907); the National Institute on Aging (AG022381, 5R01AG008122, R01 AG016495); the National Center for Alternative Medicine (RC1 AT005728-01); the National Institute of Neurological Disorders and Stroke (R01NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534, 5U01NS086625, U01NS086625, K23NS094538); National Institute of Child Health and Development (K01 HD074651-01A1) and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multiinstitutional Human Connectome Project also provided support. This research also utilized resources provided by National Institutes of Health shared instrumentation grants 1S10RR023401, 1S10RR019307, and 1S10RR023043.
Dr. Fischl has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. Dr. Fischl’s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. No other author has any disclosures.
Any opinions, findings, conclusions or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the U.S. Government, or the U.S. Department of Veterans Affairs, and no official endorsement should be inferred.
ISSN:0022-3069
1554-6578
DOI:10.1093/jnen/nlx101