Alzheimer's blood test detects disease 20 years before symptoms appear with 94% accuracy in major breakthrough
Scientists are closing in on a long-sought goal - a blood test to screen people for possible signs of Alzheimer’s disease and other forms of dementia. Researchers from Washington University School of Medicine in St. Louis now report that they have developed such a blood test that is 94% accurate in finding people with early Alzheimer’s brain changes, before the symptoms show.
According to the World Health Organization (WHO), Alzheimer's Disease is the most common form of dementia and contributes to 60–70% of such cases.
Around 50 million people have dementia globally, and there are nearly 10 million new cases every year, says the WHO. Currently, there is no treatment available to cure dementia or to alter its progressive course.
Scientists have been trying to find solutions that can target dementia at its earliest stages to prevent the formation of amyloid-beta, a protein that clogs the brains of people with Alzheimer’s.
Up to 20 years before people develop the characteristic memory loss and confusion of Alzheimer’s, damaging clumps of the protein start to build up in their brains. The blood test - which the research team says is 94% accurate when combined with age and genetic risk factor - to detect such early brain changes has moved one step closer to clinical use.
This could be a significant breakthrough in the treatment of this irreversible, progressive brain disorder, which slowly destroys memory and thinking skills, and, eventually, the ability to do simple tasks. While such a test could become available at doctors’ offices within a few years, its benefits would be much more significant once there are treatments to halt the disease process and forestall dementia, say the researchers.
In their findings, published in Neurology, the team says they can measure levels of amyloid-beta in the blood and use such levels to predict whether the protein has accumulated in the brain.
“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% accuracy. The results represent another step toward a blood test to identify people on track to develop Alzheimer's before symptoms arise,” conclude the researchers.
The findings are significant as there is growing consensus among neurologists that Alzheimer’s treatment needs to begin as early as possible, much before any cognitive symptoms arise. The reason: By the time people become forgetful, their brains are so severely damaged that no therapy is likely to heal them fully. The researchers say that testing preventive treatments require screening thousands of healthy people to find a study population of people with amyloid build-up and no cognitive problems, which is a slow and expensive process.
The current tools, such as brain scans and spinal fluid tests, are too expensive or invasive or time-consuming. According to experts, a blood test would enable doctors to intervene with clinical trials or experimental treatments at a time well before the changes have occurred in the brain and perhaps, even prevent them. With a blood test, one could potentially screen thousands of people a month, leading to faster and efficient enrollment of participants in clinical trials, and consequently, faster identification of treatments.
“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,” says the research team.
According to the team, the test might be even more sensitive than the gold standard - a PET brain scan - at detecting the beginnings of amyloid deposition in the brain.
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, says the study.
The test, which is an earlier version of the one reported two years ago, uses a technique called “mass spectrometry” to precisely measure the amounts of two forms of amyloid-beta in the blood: amyloid-beta 42 and amyloid-beta 40. The ratio of the two forms goes down as the amount of amyloid-beta deposits in the brain goes up.
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% of the time, which is promising, but not accurate enough for a clinical diagnostic test.
Accordingly, to improve the test’s accuracy, the researchers included 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. A genetic variant called APOE4 raises the risk of developing Alzheimer’s three- to five-fold. Gender also plays a role, as two out of three Alzheimer’s patients are women,” says the paper.
When these risk factors were incorporated in the analysis, they found that age and APOE4 status raised the accuracy of the blood test to 94%. Sex did not significantly affect the analysis, says the team.
“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,” state the findings.
As part of their research work, the team examined the enrollment process for a prominent Alzheimer’s prevention trial called the ‘A4’ study, which uses PET scans to confirm the presence of early Alzheimer’s brain changes in potential participants.
“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 are primarily reserved for patient care, not research studies,” say the researchers.
According to their analysis, pre-screening with a blood test followed by a PET scan for confirmation would have reduced the number of PET scans needed by two thirds. Reducing the number of PET scans could enable researchers to conduct twice as many clinical trials for the same amount of time and money, and find a solution faster, say the researchers.