Analysis of Plasma Tau as a Protein biomarker in Mild Cognitive Impairment and Alzheimer’s Disease

By Kevin Hrusovsky, Executive Chairman and CEO, Quanterix

Alzheimer’s disease is a dangerous and ultimately fatal form of dementia, and according to recent data from the Centers for Disease Control (CDC), Alzheimer’s is the sixth leading cause of death in the United States, accounting for 3.6% of all deaths. What’s more, the CDC also reports that the number of deaths from Alzheimer’s disease in the United States has risen by 55% in the last 15 years alone. With the numbers on the rise, it’s more important than ever that we continue to accelerate research to advance treatment options for this and other progressive neurodegenerative diseases.

On June 28th, Quanterix had the pleasure of hosting a webinar featuring my colleagues Dr. Henrik Zetterberg, MD, PhD Professor of Neurochemistry at the University of Gothenburg, Sweden, and at University College London, UK, as well as the Head of the Department of Psychiatry and Neurochemistry at the Sahlgrenska Academy at the University of Gothenburg, Sweden, and Dr. Jessica Gill, Investigator at National Institutes of Health (NIH) and Co-Director of the Biomarkers Core for the Center for Neurosciences and Regenerative Medicine. During the webinar, we discussed the use of ultrasensitive biomarker assays to enable the transformation of precision health, including their clinical usage in detecting and treating traumatic brain injuries and neurodegenerative diseases such as Alzheimer’s disease.

We  also had the opportunity to discuss Dr. Zetterberg’s recent Alzheimer’s research that was featured in the Journal of Alzheimer's Disease detailing the correlation between a particular type of protein and non-specific neurodegeneration. Dr. Zetterberg has been a proponent for using our Simoa technology to advance his research, as it has enabled him to see previously undetectable proteins and develop breakthrough theories.

The study, titled “Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease,” sought to determine the neuroanatomical correlates of plasma tau, a protein that has shown to be indicative of brain injuries and neurodegenerative diseases, using voxel-based analysis. Historically, peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau have been higher in Alzheimer's disease patients relative to prodromal stages and controls. While elevated CSF tau concentrations have shown an association with lower grey matter density (GMD) in Azheimer’s-specific regions in the past, this correlation has yet to be examined for plasma in a large study. Grey matter is the section of the brain responsible for a number of high-order functions, including muscle control, memory, emotions, and also sensory perceptions, and research has shown that it is more vulnerable to age-related neurodegeneration, including Alzheimer’s.

As part of their research, Dr. Zetterberg and his team collected cross-sectional data for 508 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants. The relationship between plasma tau and GMD, and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Other variables, including age and gender were also used as covariates when researchers deemed it appropriate.

After extensive analysis, Dr. Zetterberg’s team determined that plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. In addition, a negative correlation was also shown to exist between plasma tau and GMD in patients who had CSF Aβ42, less than 192 pg/mL, in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a markedly different associated brain atrophy pattern, with only a small number of overlapping regions in the fusiform gyrus. These results show that plasma tau could serve as a non-specific marker for neurodegeneration and that plasma tau is still relevant to Alzheimer’s disease; a major step forward in our quest to better understand Alzheimer’s Disease and improve how it is diagnosed and treated.

With neurodegenerative diseases like Alzheimer’s, early diagnosis is key for improving treatment options. Catching the disease early enables physicians to create a more specific treatment plan for patients, which can help slow down the progression of the disease. While treatment is important, our goal is to use findings from studies such as this, to ultimately prevent diseases before they manifest. Proteomic research, especially the analysis of protein biomarkers as predictors of disease, is paving the way for the advancement of precision medicine, and through continued investments in these types of studies, we can achieve our goal of going from a model of sick care to true preventative healthcare.