dementia-2016_scientifictracks-abstracts

10 / 46

Notes:
Page 27
Dementia 2016
September 29-October 01, 2016
Volume 6 Issue 5(Suppl) J Alzheimers Dis Parkinsonism 2016
ISSN:2161-0460 JADP, an open access journal
conferenceseries .com
September 29-October 01, 2016 London, UK
5th International Conference on
Alzheimer’s Disease & Dementia
Shahpasand K et al., J Alzheimers Dis Parkinsonism 2016, 6:5(Suppl)
AMajor Early Driver of Tauopathy and Neurodegeneration that is Blocked by Antibody
Shahpasand K1, Kondo A2, Zhou XZ2, and Lu KP2
1Royan Institute for Stem Cell Biology and Technology, Iran
2Cancer Research Institute, Boston
Traumatic brain injury (TBI) is the best-known environmental risk factor for Alzheimer’s disease (AD), whose defining
pathologic features include tauopathy made of hyperphosphorylated tau (PHF-tau) and is characterized by acute
neurological dysfunction. However, tauopathy is undetectable acutely after TBI and how TBI leads to tauopathy which in
turn would increase risk of AD is unknown. Here we identify a neurotoxic cis conformation of phosphorylated tau at Thr231
as a major early driver of TBI and neurodegeneration that is effectively blocked by the conformation specific monoclonal
antibody. We found robust cis p-tau after sport- and military-related TBI in humans and mice. Acutely after TBI in mice and
stress in vitro, neurons prominently produce cis p-tau, which disrupts axonal microtubule network and transport, spreads to
other neurons, and leads to apoptosis, a pathogenic process, which we nominated “cistauosis” that appears long before known
tauopathy. Treating TBI mice with cis antibody not only blocks early cistauosis, but also prevents tauopathy development and
spread, and restores brain histopathological and functional outcomes. These results uncover cistausosis as an early precursor
of tauopathy and an early marker of neurodegeneration after sport and military TBI. We anticipate that cis p-tau will be a
new early biomarker and that cis p-tau antibody or vaccines may be used to treat or even prevent TBI, chronic traumatic
encephalopathy and AD.
Biography
Koorosh Shahpasand has completed his PhD from Tokyo Metropolitan University in 2012, and did his postdoctoral training at Harvard Medical School on the
elucitation of cis/trans p-tau conformations during Neurodegeneration; the results of which have been published in Nature. He is now freshly employed assistant
professor at Royan Institute and supervising several research projects related to tauopathies. Notably, he has been recently awarded by a prestigous grant from
Alzheimer’s Association at Chicago.