Why did you choose to research Alzheimer’s and its detection?
Alzheimer’s disease offers incredible potential for impact. As the leading cause of disability and death in our elders, and with no effective treatments, the potential for changing the care of millions is now possible due to decades of careful scientific work.
Alzheimer’s disease is intellectually fascinating to me (Randall) as the disease is a convergence of aging and how the human mind works.
I (Nicolas) am an analytical chemist, specializing in biomolecules analysis using mass spectrometry. I had the opportunity to join research on Alzheimer's after my Ph.D. in 2012. My grandmother’s sister died from AD in 2007 and I know how devastating this disease is. I really want to use my skills to help AD research in finding a cure.
Image Credit: Atthapon Raksthaput/Shutterstock.com
Why is it important to have an accurate and reliable test for its detection? What are the limitations of the currently used PET scan for the detection of Alzheimer’s?
In order to hope to treat a disease, we have to accurately identify it. Currently, PET scans have limited availability, are expensive, and radioactive.
Can you describe how you carried out your research into designing a blood test for the detection of Alzheimer’s? How does this test work?
Our previous research in cerebrospinal fluid, the fluid surrounding the brain, has pinpointed a particular biomolecule, ptau217, as dramatically increased in AD patients. We thought ptau217 could be transferred from cerebrospinal fluid to blood and thus likely detected if an appropriate test was designed.
This test measures ptau217 but also other tau forms by mass spectrometry, a physical technique with high precision. Thus, we can differentiate our target amongst millions of others and measure the ptau217 level in plasma.
However, before injecting the blood sample into the mass spectrometer, we had to find a recipe able to clean the blood and concentrate ptau217. This was a critical step. Also, the mass spectrometer we use is one of the most sensitive ever built.
Sensitivity is key because ptau217 in the blood is found in very low abundance. To date, ptau217 is likely the lowest abundant protein modification ever measured in blood by mass spectrometry.
What is p-tau-217 and at what accuracy can the test detect this?
P is for phosphorylation, a modification, or let say a kind of tag attached to protein. This modification is made by an enzyme. Tau is one of the two proteins found as protein aggregates in the brain of Alzheimer patients.
217 is a code to find where the phosphorylation is in the tau protein.
We are totally accurate in our detection of ptau217. The mass spectrometry signal is so specific we are certain at 100% the signal is ptau 217.
Plasma tau truncation profile after chemical extraction and IP in the discovery cohort.
Do you believe that by having a simple blood test that can detect Alzheimer’s, we could potentially reduce the number of people developing this disease?
The only way to reduce this number is to find a treatment. This test could assist clinical research to speed up the process of testing drugs.
If a treatment is found in the future, the test should be helpful to screen the population and identify as early as possible an individual who would benefit from the treatment.
What further research needs to be carried out before this test can be readily available?
Refinements in high-throughput systems and commercial laboratory incorporation will be needed for this to be available.
Furthermore, we need to decrease the volume of blood needed for the test and potentially combine this test with other tests on other biomarkers to be able to predict as early as possible an abnormality linked to a risk of future Alzheimer's disease.
What are the next steps in your research?
To pursue additional studies of the relationship of blood p-tau217 and other tau and protein biomarkers of Alzheimer’s disease.
Where can readers find more information?
About Dr. Randall Bateman
Randall J. Bateman, M.D. is the Charles F. and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine.
Dr. Bateman’s laboratory investigates the causes, and future diagnoses and treatments of Alzheimer’s disease utilizing a wide variety of assays and techniques from basic applications, such as quantitative measurement of stable-isotope labeled peptides to clinical translational studies in diagnostic and therapeutic biomarkers for Alzheimer’s disease.
Dr. Bateman’s lab measures the pathophysiology of Alzheimer’s disease in humans and measures amyloid-beta isoform kinetics in Alzheimer’s disease. Dr. Bateman trains postdoctoral fellows, graduate students, and undergraduates in his lab.
About Dr. Nicolas Barthélemy
Dr. Barthélemy obtained his Ph.D. degree in Analytical Chemistry from the University of Strasbourg in France. He specializes in protein characterization and quantitation by mass spectrometry.
He joined Dr. Bateman’s laboratory at Washington University in St. Louis as Postdoctoral Associate in 2015.
As a research instructor, he is pursuing his research on tau protein implication in Alzheimer's Disease and other tauopathies. He first reported specific ptau217 changes in AD cerebrospinal fluid in 2015.