2019 Biomarkers Across Neurodegenerative Diseases Grant (BAND)

Ultrasensitive Assays for Tau and aSyn Aggregates in AD and PD

Can novel tests for measuring protein clumps help diagnose Alzheimer’s, Parkinson’s disease and other dementias?
 

Allison Kraus, Ph.D.
National Institute of Allergy and Infectious Diseases
Bethesda, MD - United States

Background

Many brain disorders, including Alzheimer’s (AD) and Parkinson’s disease (PD), are characterized by abnormal proteins in the brain. These proteins accumulate into clumps that can damage brain cell health and function. The two major hallmarks of Alzheimer’s are beta-amyloid plaques and the abnormal form of the tau protein forming tau tangles. A different protein called the alpha-synuclein that misfolds and forms clumps in the brain, is a characteristic of Parkinson’s disease. Studies show that many individuals have brain changes associated with more than one type of these misfolded proteins such as plaques, Lewy bodies and tangles, thus making a definitive diagnosis more challenging. To enable future methods of diagnosing brain diseases, researchers are investigating optimal methods that could measure multiple types of protein levels in the brain.
 

Research Plan

In preliminary research, Dr. Allison Kraus and colleagues have developed a series of tests for detecting very low levels of abnormal tau and alpha-synuclein in the brains of individuals with Alzheimer’s and Parkinson’s disease. Building on these findings, Dr. Kraus and colleagues will conduct a more thorough assessment of their protein-measuring tools. The researchers will quantify multiple proteins in the brain tissue, cerebrospinal fluid (or biological fluid surrounding the brain and spinal cord) and nasal cavity tissue (or tissue behind the nose) from people with Alzheimer’s, Parkinson’s disease and other brain diseases. Based on past studies, Dr. Kraus believes that protein clumps in the cerebrospinal fluid and nasal cavity tissue may indicate disease in the brain. Dr. Kraus believes that since disruption of sensory systems such as smell may occur early in Alzheimer’s, a noninvasive test such as nasal swipe may help in the early detection of disease.
 

Impact

If successful, this project could identify a potential method for improving the early diagnosis of Alzheimer’s, Parkinson’s and other dementias. This method could also lead to more accurately-targeted disease therapies.