A new generation of blood tests is poised to change the way doctors determine whether patients with memory loss also have Alzheimer's disease.
The tests detect substances in the blood that indicate the presence of sticky amyloid plaques in the brain — a hallmark of Alzheimer's. So these tests have the potential to replace current diagnostic procedures, like costly PET scans and uncomfortable spinal taps.
Blood tests also promise to provide doctors with a quick way to identify patients who could benefit from new drugs that remove amyloid from the brain.
But the accuracy of the tests still varies widely.
"Some of them are really good, and some of them are really bad," saysDr. Suzanne Schindler, a dementia specialist at Washington University School of Medicine in St. Louis.
The search for plaques and tangles
Blood tests represent the latest advance in efforts to detect the buildup of amyloid plaques and fibrous tangles in the brain.
"It used to be that the only way you could definitively diagnose someone with Alzheimer disease is by doing an autopsy," Schindler says.
Then, starting in the early 2000s, scientists found ways to detect plaques and tangles using PET scans and tests of spinal fluid. There are now versions of both approaches that are approved by the Food and Drug Administration.
But the scans are costly, and spinal taps are unpopular with many doctors and patients. Both also require expertise that is in short supply.
So Schindler and her colleagues got a lot of attention in 2019 when they published a paper showing that amyloid plaques could be revealed by a blood test.
"Since then, I've probably had 100 people email me wanting a test," Schindler says. "In many cases, they are people who had family members who had Alzheimer's disease, and this is their biggest fear."
Today, labs offer more than a dozen Alzheimer's blood tests.
"The technology has really developed very quickly," Schindler says. "People see the dollar signs, and it's very doable to get into the market."
That market is potentially vast because more than 6 million people in the United States have Alzheimer's and an even larger number are at risk for the disease.
FDA's lack of approval
But there's not much regulation of existing blood tests for Alzheimer's. So far, none has been approved by the FDA.
Instead they are marketed as laboratory developed tests, a special category that usually receives minimal FDA oversight. (This past October, the FDA proposeda rule that would increase scrutiny of these tests.)
For now, though, "you can have a test for Alzheimer disease that's not very good," Schindler says, "but as long as you get similar results over time you can market it."
This means that many tests, if used on the population that typically visits a dementia specialist, would misdiagnose about one in four patients, Schindler says.
And the accuracy would be worse if the tests were used on a population at lower risk, speakers told a press conference on Alzheimer's blood testing at the Society for Neuroscience meeting in November.
"When you're assessing a big group of people, a lot of whom don't have the disease, you are going to get a lot of false positives," said Keenan Walker, an Alzheimer's researcher at the National Institute on Aging at the National Institutes of Health.
That's why it's so important to use the best blood tests, says Dr. Randall Bateman, a professor of neurology at Washington University in St. Louis.
"The one we developed can be 95% accurate," he says, "so now these blood tests are rivaling the performance of the PET scans and the spinal taps that we've traditionally used."
Testing for treatment
Interest in blood tests has soared since July, when the FDA fully approved Leqembi (lecanemab), the first drug shown to slow the progression of Alzheimer's.
A second Alzheimer's drug, aducanumab, had received a limited FDA approval in 2021, and a third, donanemab, is likely to get full approval in the next few months.
"For the first time ever, right, Alzheimer's doctors are now able to treat patients with these drugs," Bateman says.
All three drugs remove amyloid from the brain. But to prescribe them, doctors need to show that amyloid plaques are present.
That needs to happen quickly, Bateman says, while a patient is still in the early stages of the disease.
"There's a time window where there's a benefit," Bateman says. "And if they're going to be treated in that time window, you almost have to have blood tests."
That's because most doctors aren't equipped to immediately offer a brain scan or a spinal tap.
The need for testing will increase if the existing Alzheimer's drugs are found to be most effective in patients who aren't yet showing any signs of memory impairment or thinking problems.
"The challenge then will be: How do we know who to treat if they don't even have symptoms?" Bateman says.
The answer, he says, will be the blood tests, which can detect brain changes long before patients develop problems with thinking and memory.
Bateman says that eventually, blood tests for Alzheimer's could even become a part of a routine doctor visit for people older than 50.
"They go into their regular doctor's office for a checkup," he says, "[and] blood pressure is checked, cholesterol is checked and a screening test for amyloid plaques is checked."
Some of the scientists at the Society for Neuroscience session agreed.
"It's likely that in the future anyone over the age of 60 will get an Alzheimer's test," said Virginia Man-Yee Lee, director of the Center for Neurodegenerative Disease Research at the University of Pennsylvania.
When that day comes, Bateman says, it will be critical to ensure that every blood test for Alzheimer's is as accurate as possible.
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