title: Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.
abstract: 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.
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Department of Biomedical Engineering and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United States.
authors.forename: Vikram
authors.initials: V
authors.lastname: Puvenna
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Brandeis University, Waltham, MA, United States.
authors.forename: Madeline
authors.initials: M
authors.lastname: Engeler
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Department of Biomedical Engineering and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United States.
authors.forename: Manoj
authors.initials: M
authors.lastname: Banjara
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Department of Biomedical Engineering and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United States.
authors.forename: Chanda
authors.initials: C
authors.lastname: Brennan
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Schreiber
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; The Ohio State University, Columbus, OH, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Dadas
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Department of Biology, Baldwin Wallace University, Berea, OH, United States.
authors.forename: Ashkon
authors.initials: A
authors.lastname: Bahrami
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; The Ohio State University, Columbus, OH, United States.
authors.forename: Jesal
authors.initials: J
authors.lastname: Solanki
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Emory University, Atlanta, GA, United States.
authors.forename: Anasua
authors.initials: A
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Biology, Baldwin Wallace University, Berea, OH, United States.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: Morris
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States.
authors.forename: Charles
authors.initials: C
authors.lastname: Bernick
authors.affiliation: Cerebrovascular Research, Cleveland, OH, United States; Department of Biomedical Engineering and Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United States.
authors.forename: Chaitali
authors.initials: C
authors.lastname: Ghosh
authors.affiliation: Flocel Inc., Cleveland, OH 44103, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Rapp
authors.affiliation: University of Rochester Medical Center, NY, United States.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bazarian
authors.affiliation: Flocel Inc., Cleveland, OH 44103, United States; Cerebrovascular Research, Cleveland, OH, United States. Electronic address: djanigro@flocel.com.
authors.forename: Damir
authors.initials: D
authors.lastname: Janigro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D020208:Brain Injury, Chronic / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D055815:Young Adult; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: American football; Blood–brain barrier; Cognitive decline; Serum markers; Traumatic brain injury