Detection of Amyloid-Beta and Tau Misfolded Oligomers in Biological Fluids of TBI and AD Patients
Abstract
Every year there are more than 40 million cases of traumatic brain injury (TBI) worldwide of different severity related to accidents, contact sports, and military duty. TBI is a very serious medical problem, which depending on the severity of the trauma may lead to headache, contusion, hemorrhage, loss of consciousness, skull fractures, loss of cerebral mass, and even death. Moreover, extensive studies have demonstrated that TBI may play a major role in initiating a chronic neurodegenerative damage, leading to the onset of devastating neurological disorders, such as Alzheimer s disease (AD) or Parkinson s disease (PD). Currently, it is not possible to monitor the changes occuring in the brain as a consequence of TBI or even less the progression of the damage into incurable neurodegenerative diseases. The main goal of this project is to develop a highly efficient biochemical test to detect the formation of misfolded protein aggregates, which are the hallmark features of AD and other neurodegenerative disorders. We have recently developed a very powerful technique to cyclically amplify this process leading to the possibility to detect minute quantities of these abnormal structures is human biological fluids, such as cerebrospinal fluid (CSF) and blood. The plan is to optimize, implement, and validate this technique using samples from animal models of AD, which were experimentally subjected to TBI as well as from human patients who suffered TBI and subsequently developed AD. Longitudinal studies will be done to investigate the appearance of misfolded protein oligomers after TBI in biological fluids, as well as to estimate sensitivity, specificity, and predictive values of the test. Finally, we will attempt to establish a correlation between the quantities of protein oligomers detectable by protein misfolding cyclic amplification (PMCA) and the severity of the clinical abnormalities and data available for imaging the formation of protein aggregates in the brain. The findings generated in this project may lay the foundation for the development of a sensitive, noninvasive, and objective laboratory test to detect diverse misfolded protein oligomers in CSF and blood plasma of people affected by TBI, which may be converting into some of the major forms of neurodegenerative diseases, including AD or PD. Such a technology might have tremendous impact on understanding the long-term consequences of TBI and enabling the biochemical diagnosis of neurodegenerative damage produced as a consequence of TBI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710559
Entities
People
- Claudio Soto
Organizations
- United States Army
- University of Texas Health Science Center at Houston