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Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy
Open accessAbstract
Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE.
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“P-tau in these regions has recently been described in the postmortem brains of patients who had ALS [31], temporal lobe epilepsy [32], and multiple system atrophy [33] but no known history of participation in contact sports or neurotrauma.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [32]
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“However, the presence of tau pathology in childhood or adolescent-onset epilepsies, such as Dravet syndrome, Nodding syndrome, Lafora disease, NPC, TSC, and ASD, and in relatively younger TLE patient cohorts (Puvenna et al., 2016; Smith et al., 2019; Gourmaud et al., 2020) suggest a causal link between seizure activity and p-tau accumulation.”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Puvenna et al., 2016
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“And in humans with chronic epilepsy, elevated p-tau is present in post-mortem (Thom et al., 2011) as well as surgically resected tissue (Puvenna et al., 2016; Tai et al., 2016; Liu C. et al., 2017; Prada Jardim et al., 2018; Smith et al., 2019; Gourmaud et al., 2020).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Puvenna et al., 2016
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“Interestingly, observations of subpial bands formed by cortical p-tau depositions have been made across separate studies (Puvenna et al., 2016; Tai et al., 2016; Smith et al., 2019), providing evidence for a novel pattern of tau pathology in TLE that may result from seizure-induced reorganization of temporal lobe networks (Tai et al., 2018).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Puvenna et al., 2016
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“In addition, it has been found in a small number of people with (1) substance abuse (24), (2) temporal lobe epilepsy (25), (3) amyotrophic lateral sclerosis (ALS) (26), (4) multiple system atrophy (22), and (5) other neurodegenerative diseases (23) who have no known participation in collision or contact sports and no known exposure to repetitive neurotrauma.”
From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [25]
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Metadata
- Authors
- Puvenna, V., Engeler, M., Banjara, M., Brennan, C., Schreiber, P., Dadas, A., Bahrami, A., Solanki, J., Bandyopadhyay, A., Morris, J. K., Bernick, C., Ghosh, C., Rapp, E., Bazarian, J. J., & Janigro, D.
- Affiliations
- Cleveland Clinic Lerner College of Medicine (US)
- Brandeis University (US)
- University of Pittsburgh (US)
- The Ohio State University (US)
- Baldwin Wallace University (US)
- Emory University (US)
- Cleveland Clinic (US)
- University of Rochester Medicine (US)
- Corresponding author
- Janigro, Damir
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 1630
- Pages
- 225-240
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4853900
- OpenAlex
- W2140341262
- Cited by
- 144
- References
- 21
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 7 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 11 · 2019: 27 · 2018: 16 · 2017: 17 · 2016: 7
- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Boston University Center
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- phosphorylated tau, chronic traumatic encephalopathy, temporal lobe epilepsy, repetitive traumatic brain injury, tau pathology, tau tangles, limbic system, postmortem brain
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Brain, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Epilepsy, Female, Humans, Immunohistochemistry, Infant, Male, Middle Aged, Phosphorylation, tau Proteins, Brain Injury, Chronic, Young Adult
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