New Diagnostic Blood Test for Alzheimer’s Disease Target Tau

(Posted on Wednesday, October 30, 2024)

A newly published study from Sweden unveiled a blood test capable of detecting Alzheimer’s disease with 90% accuracy. Although Alzheimer’s is the most common form of dementia globally, current diagnostic approaches misdiagnose more than one in four people. By measuring a specific protein, called tau, this blood test seems to accurately, and cheaply, detect key hallmarks of early neurodegeneration.

What is tau? Found exclusively in neurons, tau proteins bind to the internal skeleton-like structure of cells, known as microtubules. Tau helps microtubules distributed throughout the neuron give the cell its shape and transport nutrients and other cellular materials. Normally, only small amounts of tau can be found in the cytoplasm or the cellular fluid. Individuals with Alzheimer’s, however, develop clumps of tau in the brain, a known hallmark of the disease. Although tau accumulation seems to be secondary to the appearance of beta-amyloid plaques, another protein hallmark of Alzheimer’s, only tau correlates with impaired memory and other cognitive symptoms.

Alzheimer’s disease belongs to a family of tauopathies, a group of neurodegenerative diseases characterized by abnormal tau. The tau gene produces six distinct isoforms, or versions, of the protein based on how the protein sequence is cut. Depending on which isoforms are affected, the accumulation of tau may present as one of more than 20 different tauopathies. Alzheimer’s disease, in particular, is associated with an abnormal balance of 3R and 4R tau proteins, in which enhanced levels of 4R correlate with increased cognitive symptoms. Measuring these changes involves a complex process of tapping into the cerebral spinal fluid, a procedure not commonly used in clinical practice.

To detect Alzheimer’s disease less invasively, Palmqvist et. al instead focused on a specific form of tau: phosphorylated tau-217 or p-tau217. Previous studies have detected this protein biomarker not only in cerebrospinal fluid but also circulating in the bloodstream. Phosphorylated tau, in fact, is one of the key drivers of tauopathy in Alzheimer’s disease. Normal tau becomes phosphorylated as molecular phosphate groups are attached, which changes the protein’s structure. Misshapen tau proteins then clump together, forming aggregates within the cell. As the cell’s clean-up crew attempts to remove the clumps, a leading theory suggests that the abnormal tau induces phosphorylation in additional proteins leading to a cascade of neurodegeneration. More tau aggregates contribute to worsening cognitive function. The key to early diagnosis, therefore, is to identify subtle changes in phosphorylated tau in time to slow the progression of memory loss.

In this study, Palmqvist et. al recruited over 1200 individuals experiencing dementia-related symptoms. Each participant provided a blood sample and underwent standard clinical evaluations for Alzheimer’s disease. When measuring the percentage of phosphorylated tau, the blood test’s accuracy was greater than standard clinical evaluations alone. Investigators also found that Alzheimer’s disease was more accurately detected in individuals who had already progressed to dementia, compared to those with mild cognitive decline who were less likely to have this diagnosis regardless.

Currently, measuring phosphorylated tau-217 levels offers the highest diagnostic accuracy of any Alzheimer’s disease blood test. These findings bring us one step closer to a future where primary clinics can deploy a cost-effective and minimally invasive test for Alzheimer’s. As ongoing studies uncover the role of tau in disease progression, investigators are hopeful that a corresponding treatment may not be too far away.