CTSA News

Alzheimer’s disease, a neurodegenerative disease that affects memory and other cognitive functions, is the leading cause of dementia and affects more than 7 million people in the U.S. Recent developments for AD treatment work by removing excess amyloids, or protein aggregates that can build up to form plaques that impede brain function, from the brain. These promising therapies require accurate early AD diagnosis; they are only effective in the early stages of AD and are ineffective for those with other types of dementia. However, current diagnostic methods primarily include brain tissue examination after death and, for living patients, highly invasive procedures or expensive imaging techniques. Minimally invasive AD tests that can diagnose disease earlier could support anti-amyloid therapy use and serve a wider population of patients.

In 2021, Jerry Wang, MD, PhD, an associate professor of pathology at Duke University, and Dr. Bin Xu, a Principal Investigator at NC Central University’s Biomanufacturing Research Institute and Technology Enterprise and an associate professor of pharmaceutical sciences, started conducting research to develop minimally invasive tests (blood- and cerebrospinal fluid [CSF]-based) for earlier AD diagnosis and monitoring disease severity. Their work builds on the recent discovery of changes in tau proteins in the brain, wherein they misfold and are more likely to clump. This clumping leads to symptoms associated with various neurodegenerative diseases, including AD. However, current tests for these tau proteins can only be used on brain tissue from deceased patients to indicate if the patient was affected by AD or other neurodegenerative diseases (e.g., Pick’s disease or corticobasal degeneration) that also lead to dementia. Recent discoveries indicate that misfolded tau proteins can be found in the blood and CSF of living patients with AD, suggesting that early AD diagnosis is possible via identification and detection of AD-specific tau protein biomarkers. Xu collaborates with Ling Wu, MD, PhD, a researcher based at NC Central who is also a Duke/University of North Carolina (UNC) Alzheimer’s Disease Research Center (ADRC) Research Education Core (REC) Scholar. This team first identified several potentially AD-specific tau protein biomarkers through experiments wherein they examined brain tissue from deceased individuals with and without AD. Next, Dr. Wang’s team validated these biomarkers by training machine learning software to recognize misfolded tau proteins. Wang and Xu were able to demonstrate that these biomarkers can be used to differentiate AD from other neurodegenerative diseases with similar tau protein behavior and to identify samples with AD-specific mild cognitive impairment, an early stage of AD where cognitive impairment does not interfere with day-to-day life yet. In another study, Andy Liu, MD, MS, an associate professor of neurology at Duke, joined the joint research team to further examine whether one of these identified tau protein biomarkers was sufficient for diagnosing early-stage AD. Using a laboratory test for this biomarker, CSF, and plasma samples from living patients, the joint research team demonstrated that this biomarker could differentiate early-stage AD from cognitively normal participants. However, more work is needed to differentiate early-stage AD from non-AD cognitive impairment. This research program has led to several invention disclosures and Patent Cooperation Treaty (PCT) applications, which support patent applications within the US and internationally. The joint research team is now validating ultrasensitive minimally invasive tests they have developed to identify the presence of these biomarkers in early-stage AD. This work paves the way for earlier and cost-effective detection of AD, which will facilitate treatment.