Shih-Hsiu "Jerry" Wang, MD, PhD, associate professor of pathology at Duke and neuropathology core lead for the Duke-University of North Carolina at Chapel Hill Alzheimer's Disease Research Center (ADRC), has been awarded a two-year, $1.28-million R56 grant from the National Institutes of Health (NIH) to develop new biomarkers for the diagnosis of limbic-predominant age-related TDP-43 encephalopathy (LATE).
The grant, titled "New Biomarkers for LATE Diagnosis and Differentiation from AD Dementia," represents a collaborative effort among Wang; Bin Xu, PhD, of North Carolina Central University; and Peter Nelson, MD, PhD, of the University of Kentucky.
LATE is a common age-related neurodegenerative disease that can cause memory loss and cognitive impairment much like Alzheimer's disease (AD). However, unlike Alzheimer's disease, there are currently no reliable biomarkers to diagnose LATE in patients, creating a significant obstacle to more accurately classify patients based on the underlying cause of their dementia and developing targeted therapies.
To address this challenge, Wang and collaborators have developed a novel TDP-43 seed amplification assay (SAA) using human brain tissue and cerebrospinal fluid (CSF) samples from the Duke Bryan Brain Bank and Biorepository. The assay is designed to detect pathological TDP-43 protein aggregates, a defining feature of LATE.
“Our team believes that these tools, when combined with a complementary tau seed amplification assay, may help distinguish patients whose dementia is driven by Alzheimer's disease, LATE, or a combination of both conditions,” said Wang.
The new NIH funding will allow the team to optimize and validate both assays in a larger patient cohort, including cerebrospinal fluid samples collected during life from patients later confirmed at autopsy to have LATE neuropathological changes. Researchers also plan to explore how TDP-43 and tau SAAs can be integrated with existing Alzheimer's disease biomarkers to improve the diagnosis and differentiation of dementia during life.
The research brings together investigators from Duke, North Carolina Central University, and the University of Kentucky to address a critical unmet need in dementia diagnosis. Leveraging resources from the Duke Bryan Brain Bank and Biorepository, the team aims to develop tools that enable earlier and more accurate identification of the underlying causes of dementia.
As the prevalence of neurodegenerative diseases continues to grow, advances in biomarker development may help clinicians improve diagnostic accuracy, guide more personalized care, and ultimately improve outcomes for patients and families.