Development of in vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

2014 ◽  
Author(s):  
David L. Brody ◽  
Marc I. Diamond
2019 ◽  
Vol 11 (508) ◽  
pp. eaaw1993 ◽  
Author(s):  
Nikos Gorgoraptis ◽  
Lucia M. Li ◽  
Alex Whittington ◽  
Karl A. Zimmerman ◽  
Linda M. Maclean ◽  
...  

Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans. We examined PET data in relation to markers of neurodegeneration in the cerebrospinal fluid (CSF), structural magnetic resonance imaging measures, and cognitive performance. Cerebral flortaucipir binding was variable, with many participants with TBI showing increases in cortical and white matter regions. At the group level, flortaucipir binding was increased in the right occipital cortex in TBI when compared to healthy controls. Flortaucipir binding was associated with increased total tau, phosphorylated tau, and ubiquitin carboxyl-terminal hydrolase L1 CSF concentrations, as well as with reduced fractional anisotropy and white matter tissue density in TBI. Apolipoprotein E (APOE) ε4 genotype affected the relationship between flortaucipir binding and time since injury, CSF β amyloid 1–42 (Aβ42) concentration, white matter tissue density, and longitudinal Mini-Mental State Examination scores in TBI. The results demonstrate that tau PET is a promising approach to investigating progressive neurodegeneration associated with tauopathy after TBI.


Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1487
Author(s):  
Hadeel Alyenbaawi ◽  
W. Ted Allison ◽  
Sue-Ann Mok

The accumulation of tau protein in the form of filamentous aggregates is a hallmark of many neurodegenerative diseases such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). These dementias share traumatic brain injury (TBI) as a prominent risk factor. Tau aggregates can transfer between cells and tissues in a “prion-like” manner, where they initiate the templated misfolding of normal tau molecules. This enables the spread of tau pathology to distinct parts of the brain. The evidence that tauopathies spread via prion-like mechanisms is considerable, but work detailing the mechanisms of spread has mostly used in vitro platforms that cannot fully reveal the tissue-level vectors or etiology of progression. We review these issues and then briefly use TBI and CTE as a case study to illustrate aspects of tauopathy that warrant further attention in vivo. These include seizures and sleep/wake disturbances, emphasizing the urgent need for improved animal models. Dissecting these mechanisms of tauopathy progression continues to provide fresh inspiration for the design of diagnostic and therapeutic approaches.


2019 ◽  
Vol 59 (1) ◽  
pp. 247-252 ◽  
Author(s):  
Chunyan Li ◽  
Wanfei Li ◽  
Huanhuan Liu ◽  
Yejun Zhang ◽  
Guangcun Chen ◽  
...  

2014 ◽  
Vol 31 (14) ◽  
pp. 1277-1291 ◽  
Author(s):  
Elizabeth Steuer ◽  
Michele L. Schaefer ◽  
Leonardo Belluscio

2006 ◽  
Vol 39 (6) ◽  
pp. 1086-1095 ◽  
Author(s):  
Philip V. Bayly ◽  
Erin E. Black ◽  
Rachel C. Pedersen ◽  
Elizabeth P. Leister ◽  
Guy M. Genin

Sign in / Sign up

Export Citation Format

Share Document