Alzheimer’s is a disease that can take hold in the brain long before symptoms, like memory and cognitive decline, become evident. This makes it a very tricky one to diagnose early in the piece, but a new breed of blood tests are emerging that could change the game in this regard. The latest centers on a new biomarker in the blood, which was shown to distinguish healthy patients from early asymptomatic Alzheimer’s patients with a high degree of accuracy.
While there is a lot we are yet to understand about what causes Alzheimer’s and how it affects the brain, there are a couple of key culprits that research continues to implicate in the process. One is the amyloid beta protein that accumulates in the brains of Alzheimer’s patients in the form of toxic plaques, which previous experimental blood tests have focused on with very promising results.
Another is tau proteins, with certain variations shown to present in the cerebrospinal fluid of Alzheimer’s patients with amyloid plaque buildup. Sampling the cerebrospinal fluid involves an expensive and invasive spinal tap, but innovative blood testing techniques could offer a much simpler way forward.
This is because some of the proteins in the fluid can spill over into the blood. Back in March we looked at a blood test that leverages this physiological process to uncover a promising new biomarker in the protein p-tau181, which was found in the blood at 3.5 times the concentration of healthy controls.
The new research was carried out by a research group at Washington University School of Medicine in St. Louis, which last year published research on an Alzheimer’s blood test based on amyloid beta biomarkers that boasted an impressive accuracy of 94 percent. The team’s latest test doesn’t quite offer the same level of precision just yet, but does bring a new biomarker into the fold in the form of phosphorylated tau 217 (p-tau217).
The team started by looking at blood samples and brain scans from 34 Alzheimer’s patients. Nineteen of those had no amyloid in their brains, five had amyloid plaques but no cognitive symptoms, and 10 had both amyloid buildup and cognitive symptoms. The team found that those with amyloid in their brains exhibited levels of p-tau217 that were two to three times higher than those without amyloid, even in the subjects with no cognitive symptoms of the disease.
In a follow-up experiment, the team performed another analysis, this time of blood taken from another group of 92 patients. Forty-two had no amyloid in their brains, 20 did but had no cognitive symptoms, while 30 had both amyloid and symptoms. Higher levels of p-tau217 were found to correlate with amyloid in the brain with an accuracy of more than 90 percent. Applied to the group with no cognitive symptoms, the blood test distinguished these early, asymptomatic forms of the disease from healthy controls with 86-percent accuracy.
“This is just an exploratory study, but we think phosphorylated tau 217 is a promising target for an early diagnostic test,” Barthélemy says. “There was a large difference between the amyloid-positive and amyloid-negative groups, even amongst people who were cognitively normal. We did have to use a large volume of blood in this study, but we’re working on reducing the volume. Once we improve the way we are preparing and concentrating the sample, we will be a step closer to developing a tau-based blood test that can identify people at risk of developing Alzheimer’s dementia before symptoms arise.”
In a separate study also published today, a team from Sweden is also reporting promising results from research into p-tau217 levels in the blood. This involved analysis of 1,402 subjects, with the researchers finding that the protein could be used to distinguish Alzheimer’s patients from other neurodegenerative disorders with an accuracy of between 89 and 98 percent.
There is work to do before this type of test enters clinical use, but when considered alongside similar advances being made in blood-testing for Alzheimer’s disease, the results are certainly promising.
“I think we are now seeing convincing evidence that blood tests really can identify Alzheimer’s disease with high sensitivity – and I believe we will see these entering clinical practice rapidly,” says Nick Fox, Professor of Clinical Neurology at University College London, who was not involved with the studies. “They have the potential to extend and “democratize” biomarker-supported diagnosis in dementia with wide applicability including in low resource settings. These papers provide robust evidence of the ability of plasma p-tau to identify Alzheimer’s disease and, importantly, to discriminate it from other causes of cognitive decline.”