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conferenceseries.com
Volume 8 Journal of Alzheimers Disease & Parkinsonism
ISSN: 2161-0460 Euro Dementia 2018
May 24-25, 2018
May 24-25, 2018 | Vienna, Austria
11th International Conference on
Alzheimers Disease & Dementia
Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy
Xiao Zhen Zhou1,2,3, Onder Albayram1,2,3, Asami Kondo 1,2,3, Rebekah Mannix4, Colin Smith5, Cheng-Yu Tsai1,2,3 and Chenyu Li1,2,3
1Harvard Medical School
2Beth Israel Deaconess Medical Center
3Center for Life Science
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.
Results
Here we used cis P-taumAbs to demonstrate the presence of, and specifically eliminate, pathogenic cis P-tau in clinically relevant
in vitro and in vivo models of sport- and military-related TBI. We detected robust cis P-tau signals after sport- and military-
related TBI in humans and mice, and in stressed neurons. Following TBI or neuronal stress, cis P-tau induces cistauosis well
before previously identified tauopathy is apparent. Treating TBI mice with cis mAb ablates cis P-tau and eliminates cistauosis,
prevents the development of widespread tauopathy and restores histopathological and many functional outcomes of TBI.
Cistausosis is an early precursor of previously described tauopathy and an early marker of neurodegeneration that can be
blocked by cis mAb. We previously showed that cis P-tau has an early pathological role in Alzheimer’s disease27–34,42. Our
current data provide a direct link from TBI to CTE and Alzheimer’s disease, and suggest that cistauosis is a common early
disease mechanism in TBI, CTE and Alzheimer’s disease, and that cis P-tau and its mAb may be useful for early diagnosis,
prevention and therapy for these devastating diseases. Atlanta (GA): Centers for Disease Control and Prevention.
J Alzheimers Dis Parkinsonism 2018, Volume 8
DOI:10.4172/2161-0460-C3-043