You may have read reports about a new blood test to detect early brain changes that can flag common markers of Alzheimer’s disease. It’s moved one step closer to clinical use and could be a game-changer, according to researchers.
Up to two decades before people develop the characteristic memory loss and confusion of Alzheimer’s disease, damaging clumps of protein start to build up in their brains. Researchers from Washington University School of Medicine in St. Louis say they can measure levels of the protein amyloid beta in the blood and use the results to predict whether the protein has accumulated in the brain. Amyloid beta is considered a hallmark of the disease.
“Right now we screen people for clinical trials with brain scans, which is time-consuming and expensive, and enrolling participants takes years,” said Randall J. Bateman, M.D., senior author on the study and a WUSL professor of neurology “But with a blood test, we could potentially screen thousands of people a month. That means we can more efficiently enroll participants in clinical trials, which will help us find treatments faster, and could have an enormous impact on the cost of the disease as well as the human suffering that goes with it.”
When blood amyloid levels are combined with two other major Alzheimer’s risk factors – age and the presence of the genetic variant APOE4 – people with early Alzheimer’s brain changes can be identified with 94 percent accuracy, the study found.
Researchers say the findings, published in the Aug. 1 edition of the journal Neurology, represent another step toward a blood test to identify people on track to develop Alzheimer’s before symptoms arise. The test may be even more sensitive than the gold standard – a PET brain scan – at detecting the beginnings of amyloid deposition in the brain.
Clinical trials of preventive drug candidates have been hampered by the difficulty of identifying participants who have Alzheimer’s brain changes but no cognitive problems. The blood test could provide a way to efficiently screen for people with early signs of disease so they can participate in clinical trials evaluating whether drugs can prevent Alzheimer’s dementia. If successful, it could eventually be available at physicians’ offices and become part of routine screening for older adults.
As Time reported, “One challenge in developing a treatment for Alzheimer’s lies in that by the time symptoms occur, brain neurons have already been damaged, perhaps beyond repair. And once neural connections are compromised, they aren’t likely to reform or rebuild. Drug treatments that start after people report declines in their thinking skills may simply be too little too late.” But many drug trials which looked promising in early phases, have not been proven viable, Or, as Gina Kolata’s 2018 story in the New York Times noted, “the math is getting ugly.” The BBC put its own spin on this news by using U.K. statistics and interviewing dementia experts there.
Stat News highlighted several promising blood tests discussed at July’s Alzheimer’s International Conference. Other recent stories have looked at studies being conducted by the National Institute on Aging, by researchers in Japan, and by scientists in Singapore. So far, they have all involved small cohorts.
The current study involved 158 adults over age 50. All but 10 of the participants in the new study were cognitively normal, and each provided at least one blood sample and underwent one PET brain scan. The researchers classified each blood sample and PET scan as amyloid positive or negative, and found that the blood test from each participant agreed with his or her PET scan 88 percent of the time, which is promising, but not accurate enough for a clinical diagnostic test.
To improve the test’s accuracy, researchers incorporated several major risk factors for Alzheimer’s. Age is the largest known risk factor; after age 65, the chance of developing the disease doubles every five years, according to the Alzheimer’s Association. The APOE4 raises the risk of developing Alzheimer’s three- to fivefold. And gender also plays a role: Two out of three Alzheimer’s patients are women.
When the researchers included these risk factors in the analysis, they found that age and APOE4 status raised the accuracy of the blood test to 94 percent. Gender did not significantly affected the analysis.
The results of some people’s blood tests initially were considered false positives because the blood test was positive for amyloid-beta, but the brain scan came back negative. But some people with mismatched results tested positive on subsequent brain scans taken an average of four years later. The finding suggests that, far from being wrong, the initial blood tests had flagged early signs of disease missed by the gold-standard brain scan.
There is growing consensus among neurologists that Alzheimer’s treatment needs to begin as early as possible, ideally before any cognitive symptoms arise. By the time people become forgetful, their brains are so severely damaged no therapy is likely to fully heal them. But testing preventive treatments requires screening thousands of healthy people to find a study population of people with amyloid build-up and no cognitive problems, a slow and expensive process.
As part of the study, the researchers analyzed the enrollment process for a prominent Alzheimer’s prevention trial called known as the A4 study that used PET scans to confirm the presence of early Alzheimer’s brain changes in potential participants. They concluded that prescreening with a blood test followed by a PET scan for confirmation would have reduced the number of PET scans needed by two thirds. Unlike blood tests, which cost a few hundred dollars, each PET scan costs upward of $4,000. A single site can only run a few dozen PET brain scans a month because PET scanners primarily are reserved for patient care, not research studies.
According to Bateman, 10,000 people would need to undergo screening to get 1,500 to 2,000 qualified individuals for a prevention trial. Reducing the number of PET scans could enable researchers to conduct twice as many clinical trials for the same amount of time and money.
Resources
This fact sheet from the National Institute on Aging provides an easy-to-understand explanation of biomarkers and tests for dementia.
Not all cognitive decline is Alzheimer’s disease. We recently reported on LATE dementia, which often mimics some Alzheimer’s symptoms but affects a different brain protein.
There’s still no viable treatment for Alzheimer’s. So journalist Linda Marsa looked at some alternative therapies in this How I Did it.
