title: Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.
abstract: Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer's disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term 'cistauosis', appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer's disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury.
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Asami
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Koorosh
authors.initials: K
authors.lastname: Shahpasand
authors.affiliation: Division of Emergency Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Mannix
authors.affiliation: Division of Emergency Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Juliet
authors.initials: J
authors.lastname: Moncaster
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Chun-Hau
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Yandan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Harvard Medical School, Boston, MA, 02130.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Driver
authors.affiliation: Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wei
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Luo
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Onder
authors.initials: O
authors.lastname: Albayram
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rotenberg
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.affiliation: Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.affiliation: Alzheimer's Disease Center, CTE Program, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Micheli Center for Sports Injury Prevention, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: William
authors.initials: W
authors.lastname: Meehan
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Xiao Zhen
authors.initials: XZ
authors.lastname: Zhou
authors.affiliation: Division of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.|Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Kun Ping
authors.initials: KP
authors.lastname: Lu
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology* / Q000627:therapeutic use; D000915:Antibody Affinity; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000633:toxicity; D013312:Stress, Physiological; D024801:Tauopathies / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology / Q000633:toxicity
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D010750:Phosphoproteins; D016875:tau Proteins