Duke Pathology’s Shih-Hsiu “Jerry” Wang, MD, PhD, and Bin Xu, PhD, an assistant professor at North Carolina Central University (NCCU) have been awarded a Translational Research grant from NC Biotechnology Center.
The grant awards $100,000 over the course of 18 months to support their collaborative project titled “Misfolded Tau Based Biomarkers for Diagnosing and Differentiating Alzheimer’s disease (AD) and Alzheimer’s disease and related dementias (ADRD).” They will use the funding to translate findings from the lab to diagnostic assays with commercial potential.
AD is a clinical pathological entity characterized by clinical symptoms of amnestic dementia and confirmed at autopsy by the presence of amyloid plaques and neurofibrillary tangles. However, recent development of disease-modifying therapies underscores the importance of identifying patients with plaques and tangles at early stages of Alzheimer’s disease before symptoms become irreversible.
Tau is a microtubule-associated protein (MAP) that is predominantly expressed in the axons of neurons. Tau aggregates are present in multiple neurodegenerative diseases known as "tauopathies," including AD, Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Such misfolded tau aggregates are therefore potential sources for tauopathy biomarker discovery.
The proposal builds on their previous work, “Selective Detection of Misfolded Tau From Postmortem Alzheimer's Disease Brains;” and “Site-Specific Phospho-Tau Aggregation-Based Biomarker Discovery for AD Diagnosis and Differentiation.” In those projects, they used real-time quaking-induced conversion (RT-QuIC), a very sensitive assay commonly used for diagnosis of human prion diseases. As tau aggregation is driven by phosphorylation and other protein post-translational modifications, they also used antibodies directed against phospho-tau at specific sites commonly found in AD patients to differentiate AD brains from normal controls and to differentiate AD from other tauopathies such as PSP and CBD.
Other key team members include Xu Lab member Ling Wu, MD, PhD, Duke Neurologist Andy Liu, MD, MS, and project manager Promila Pagadala, PhD, with Duke Clinical & Translational Science Institute (CTSI).