The test developed at Washington University, which is likely years away from clinical use, tests for amyloid in the blood—if the blood amyloid levels are very low, it’s possible that the individual may have amyloid plaques in the brain.
One of the many problems facing researchers working to develop treatments for Alzheimer’s disease is the lack of good diagnostic tests. Although there are some biomarkers, such as ApoE4, that show a connection to the disease, they are not reliable predictors or diagnoses. Even physician diagnosis is suspect—some studies have shown that community doctors only diagnose Alzheimer’s accurately 50 to 60% of the time, which is roughly equivalent to a coin-toss.
Researchers at Washington University in St. Louis have developed a high-precision assay that can accurately identify amyloid in the brain using immunoprecipitation and liquid chromatography-mass spectrometry. One of the problems that immediately comes to mind about this test is the current unanswered questions about amyloid in the brain and its role in Alzheimer’s disease.
For the last several decades, researchers have focused on clearing or preventing the accumulation of amyloid, a type of protein, from accumulating in the brain, because it was thought that the disease was caused by clumping of this protein. Unfortunately, most researchers have concluded that this is ineffective. Current thinking is that amyloid accumulation definitely plays a role in the disease, but in and of itself is not the cause of the disease. It is, however, a significant risk factor, and a blood test that can identify amyloid deposits before brain scans do would be beneficial for physicians diagnosing the disease and for biopharma companies conducting clinical trials.
The test developed at Washington University, which is likely years away from clinical use, tests for amyloid in the blood—if the blood amyloid levels are very low, it’s possible that the individual may have amyloid plaques in the brain. Suzanne Schindler, first author of the paper, told The New York Times that the reason for that is that amyloid is “sticky.” When it accumulates in the brain, levels drop in the blood.
The Washington University study looked at 158 volunteers who were generally in their 60s and 70s. Most were cognitively normal. They were periodically tested for cognition and memory, received spinal taps and brain scans. Schindler and her research team used their test on the patients’ stored blood to test for beta amyloid. Then they compared what they found with the results of PET scans that the patients had taken over a period of years.
They also correlated the test results with other Alzheimer’s risk factors, such as age and ApoE4. The results were the blood test was accurate 94% of the time in predicting the presence of amyloid plaques in the brains of people, even when they were mostly asymptomatic.
Presence of amyloid by itself is not a complete predictor of Alzheimer’s. There are people with clumps of amyloid who do not show signs of the disease. However, this test shows promise as a screening tool, particularly for the use of clinical trial researchers.
Michael Weiner, a neurologist at the University of California, San Francisco, told The New York Times, “If you are doing a prevention trial, you are looking for evidence of the disease that is silent.”
Approximately 25% of people in their mid-70s begin accumulating amyloid plaques, but their cognition and memory is largely intact. A PET scan runs about $5,000, and a clinical trial looking to recruit 1,000 patients could run up $25 million in PET scans alone trying to find the trial population. A blood test would cost significantly less.
There’s been a recent increase in focus on developing diagnostic tests for Alzheimer’s. In April, Bill Gates, Jeff Bezos and MacKenzie Bezos teamed up to donate over $20 million to the Diagnostics Accelerator, a project that is part of the Alzheimer’s Drug Discovery Foundation (ADDF). The accelerator’s mission is to develop an easy and affordable test for Alzheimer’s disease.
On his blog, GatesNotes, Bill Gates outlined current advances in diagnosing Alzheimer’s, usually via a spinal tap or a brain scan, which are both invasive and expensive. People don’t typically look for diagnoses for the disease until they start showing symptoms.
“It’s hard to overstate how important finding a reliable, affordable, and easy-to-use diagnostic is for stopping Alzheimer’s,” Gates wrote.
Hopefully the new test is a step in the right direction.
