Conference Coverage

Blood test might rival PET scan for detecting brain amyloidosis



A blood test that seems almost as good as amyloid PET scanning, the gold standard, for detecting asymptomatic amyloid plaques in the brain could be on the market in 2-3 years, according to a report at the annual meeting of the American Neurological Association. The research was also published in Neurology (2019 Oct 22;93[17]:e1647-59).

Dr. Suzanne Schindler of Washington Univesity, St. Louis

Dr. Suzanne Schindler

Investigators at Washington University, St. Louis, found that, among 158 mostly cognitively normal people in their 60s and 70s, the plasma ratio of amyloid-beta 42 peptide to amyloid-beta 40 peptide identified people who were PET positive and PET negative for amyloid with an area under the curve of 0.88 (95% confidence interval, 0.82-0.93) and climbed to 0.94 when combined with age and Apolipoprotein E epsilon 4 status (95% CI, 0.90-0.97), “which is really quite spectacular for a blood test,” said study lead Suzanne Schindler, MD, PhD, who is affiliated with the university.

People who had a positive blood test – a ratio below .1281 – but a negative PET scan were 15 times more likely to convert to a positive scan at an average of 4 years than subjects with a negative test. “The blood test [detected] brain changes of Alzheimer’s disease before the amyloid PET scan,” Dr. Schindler said.

Amyloid-beta 42 – the number refers to how many amino acids are in the peptide chain – is much stickier and more prone to aggregate in plaques than amyloid-beta 40. The ratio of the two falls as the 42 form is sequestered preferentially into amyloid plaques while the level of amyloid-beta 40 remains more constant, she explained at the meeting.

The team concluded that the test accurately “predicts current and future brain amyloidosis” and “could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia.”

“We are really excited about it. I think there’s been recognition for a long time that a blood test would really be a game changer. We still have a little bit more work to do, but I don’t think it’s that far away,” Dr. Schindler said in an interview after her presentation.

The goal of Alzheimer’s research is to slow, reverse, or even prevent brain pathology before symptoms set in, at which point damage is likely irreversible. For that to happen, plaques need to be detected early.

Currently there are two ways to do that, both with difficulties: PET scans, which are expensive, expose people to radiation, and of limited availability, and spinal fluid analysis, which involves a lumbar puncture that “not many people want to undergo.” The problems slow down enrollment for prevention trials, Dr. Schindler said.

The blood test, which the Food and Drug Administration granted breakthrough status in January 2019, could offer a much easier and less expensive way to identify subjects and monitor outcomes. It could “really speed up enrollment and help us get to effective drugs faster,” she said.

Beyond that, clinicians could use it to help figure out what’s going on in older people with cognitive issues. If a drug or some other way is ever found to prevent Alzheimer’s, there’s even the possibility of screening patients for amyloidosis during routine exams. Potentially, “I think the market is huge,” she said.

The test is being developed by a company, C2N diagnostics, founded by Dr. Schindler’s colleagues at the university, and could be available commercially in 2-3 years. It involves high precision immunoprecipitation and liquid chromatography/mass spectrometry, so “it isn’t something your general lab is going to do. It’s probably going to be a couple centers that have this test, and everybody mails their samples in, which we do for a lot of different tests,” she said.

Several companies are working on similar assays.

Dr. Schindler said she has no financial stake in the blood test.

SOURCE: Schindler S et al. Neurology. 2019 Oct 22;93(17):e1647-59.

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