Selective Detection of Pathological Alzheimer’s Disease (AD)-Tau in Human Biofluids
There are currently no blood tests to determine if a person has Alzheimer’s disease. It can be difficult to determine whether a person with dementia has Alzheimer’s disease, a different neurodegenerative disease, or both simultaneously. We created new antibody, named GT-38, that detects a form of tau protein present in Alzheimer’s disease but not other neurodegenerative diseases. We will use GT-38 to develop a test for blood or cerebral spinal fluid to distinguish Alzheimer’s disease from other neurodegenerative diseases.
The goal of my research is to develop a blood test to detect Alzheimer’s disease. In the brains of patients with Alzheimer’s disease, tangles made of tau protein form within neurons and are associated with decreased cognitive function and neuronal death. In my recent work we created an antibody, named GT-38, that specifically detect the form of tau present in tangles. This is important because current tests of cerebrospinal fluid (CSF) can detect tau which is released from dying neurons but is not necessarily the result of Alzheimer’s disease and may be a result of traumatic brain injury or other neurodegenerative diseases. In the work funded by BrightFocus I am using GT-38 to detect only the Alzheimer’s disease form of tau in CSF and adapting the antibody to ultrasensitive tests so that we can hopefully detect Alzheimer’s disease tau in plasma. This research aims to generate a blood-based test for Alzheimer’s disease to address a major unmet need for clinical trial enrollment and provide a biological readout of disease progression to test the effectiveness of new drugs to treat Alzheimer’s disease.
About the Researcher
Garrett Gibbons is a postdoctoral fellow at the Center for Neurodegenerative Diseases Research (CNDR) at the University of Pennsylvania mentored by Drs. John Trojanowski and Virginia Lee. He earned his PhD in the Department of Molecular and Cellular Pathology at the University of Michigan and his Bachelor of Sciences in Pharmaceutical Chemistry from Michigan Technological University. Dr. Gibbons has a strong interdisciplinary background from screening small molecules and synthetic organic chemistry to chemical biology approaches dissecting signaling pathways in cellular models. His postdoctoral training has focused on neuropathology, developing novel tau antibodies, and using mouse models of Alzheimer’s disease (AD) to study the cell-to-cell transmission of tau protein. Since joining the CNDR at the University of Pennsylvania, Dr. Gibbons has generated a novel conformation-selective tau antibody that detects AD-tau pathology but not tau aggregates in other primary tauopathies and has utilized this tool to investigate the contribution of co-morbid AD in study of post-mortem tissue from 180 cases of frontotemporal lobar degeneration with tau (FTLD-tau). His research focuses on development of AD-specific biomarkers, engineering tau antibodies as immunotherapy candidates for AD, and seeking novel therapeutic targets for treatment of AD.
As a teenager, I remember when my grandfather could not find his way home from the store, traveling a route he’d driven hundreds of times. I learned later that he retired from his sign company because he could no longer keep numbers in his memory and had problems with basic math and finances. He was suffering from the early stages of Alzheimer’s disease and as his condition deteriorated, I witnessed the ripple effect his illness had on our whole family, especially my grandmother, my five aunts and uncles, and many cousins. Ultimately Alzheimer’s disease ravages my grandfather’s brain and made him unrecognizable as the man he once was to our family, stripping his ability to speak and carry out even basic functions of everyday life. Based on these experiences, I vowed to work towards finding a cure to this devastating disease. I have systematically trained in chemistry, cell biology, and neuropathology to develop a multidisciplinary skill set in order to achieve this ambitious goal. In moments of doubt and disappointment, I am fortified by the nobility of the cause to end Alzheimer’s disease and I am so grateful to BrightFocus for sharing the same vision and providing support for this essential work.
First published on: November 12, 2019
Last modified on: May 6, 2020