Qinwen Mao
Professor of Pathology and Director of Neuropathology
Neurobiology of Disease
Cellular Neuroscience
Molecular Neuroscience
E-mail:
Education:
MD 1989, MS 1992, PhD 1997, Fourth Military Medical University; Postdoctoral Fellow 2001, University of Iowa Carver College of Medicine; Residency 2007, Clinic Fellow 2009, University Of Texas Southwestern Medical School
RESEARCH:
Pathogenesis and management of Alzheimer’s disease; frontotemporal lobar degeneration; Chronic traumatic encephalopathy; Biomarker development for dementia
Research Summary
My lab woks on fluid biomarkers for dementia. Currently we focus on the fluid biomarkers for TDP-43 proteinopathy. The public health impact of TDP-43 (TAR DNA binding protein of 43 kDa) proteinopathy is estimated to be on the same order of magnitude as that of Alzheimer’s disease (AD). TDP-43 was first associated with frontotemporal lobar degeneration (FTLD), the second most common cause of dementia in patients under 65. TDP-43 was later shown to be present in up to 60% of brains with AD, the most common cause of dementia. TDP-43 pathology is heterogeneous in FTLD-TDP and is associated with multiple dementia syndromes, which complicates FTLD-TDP diagnosis in living patients. These patients, who present with a wide range of associated clinical symptoms, are underserved, as their complex clinicopathologic heterogeneity leads to uncertainty surrounding their diagnosis. A major hurdle in elucidating the clinicopathologic relationships between dementia syndromes and specific markers of FTLD-TDP is the heterogeneous molecular species of the TDP-43 inclusions. More specifically, some TDP-43 species are pathologic, while some are not. Similarly, TDP-43 pathology in AD is heterogeneous, and the AD TDP types’ associations with the different molecular species of TDP-43 and neurodegeneration are unknown. Our research focuses on developing biomarkers to elucidate the clinicopathologic relationship in FTLD-TDP and AD.
A second project is focused on discovering common neuroinflammatory pathways in traumatic brain injury (TBI) and neurodegenerative disease. TBI is a growing public health threat. The CDC estimates nearly 3 million people sustain a TBI each year in the United States, contributing to over 30% of all injury related deaths. The impact of TBI is highlighted not only by its high mortality rate but also by the significant long-term complications suffered by its survivors with the progressive development of motor, cognitive, and behavioral disorders termed Chronic Traumatic Encephalopathy (CTE). Even subconcussive events, those resulting in subclinical brain dysfunction without the typical symptoms of concussion, may lead to long-term neurologic impairment. CTE is a progressive neurodegenerative disease that occurs years to decades after prior episodes of TBI, often in the context of contact sports but also in military personal exposed to blast injury from explosive devices. TBI triggers a robust pro-inflammatory response within the injured brain. Even after the acute inflammatory response has resolved several studies demonstrated residual long-lasting inflammation within the brain in both animal models as well as in patients. One of the main drivers of this continued inflammation is the persistence of activated microglia. We are determining the role of constitutive microglial activation in the etiology and evolution of both TBI and chronic neurodegenerative disease.