Update (April 21, 2022): In research published today in JAMA Network Open, C2N Diagnostics scientists and their colleagues report that the company’s blood test had an overall accuracy of 81 percent in predicting whether adults with cognitive impairment would show amyloid plaques on a PET scan.
The first blood test designed to assist physicians in determining whether a patient has Alzheimer’s disease is now available in most US states, the company C2N Diagnostics announced October 29. The test measures biomarkers that frequently reflect the presence of amyloid plaques in the brain—a hallmark of Alzheimer’s—as well as the presence of a gene variant that increases the risk of the disease.
“I’m very excited about it,” says Suzanne Schindler, a neurologist at the Washington University School of Medicine in St. Louis who was involved in testing an earlier version of the assay but is not connected to C2N. While there are two other tests for Alzheimer’s-associated brain changes, she notes, both have logistical and financial challenges: one that collects biomarkers in the cerebrospinal fluid (CSF) requires a spinal tap, while the other, a scan called amyloid PET, involves injecting a radioactive tracer, costs thousands of dollars, and is only performed at specialized centers. “I think patients really like the idea of a blood test,” she says. “And I think that it really has the potential to allow us to do a lot more testing than we have done in the past.”
The price of the test is $1,250, says C2N CEO Joel Braunstein, but patients who qualify for financial assistance will be charged between $25 and $400. Health insurance companies don’t currently pay for the test, he adds, but qualifying for this reimbursement “is a very high priority” for the company.
“If you asked me [five or ten] years ago if there would ever be a blood test for Alzheimer’s, I would have been very skeptical,” says Howard Fillit, the executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, which invested in C2N’s development of the test. “So the fact that this is on the market now is just amazing.”
Fillit wasn’t alone in thinking that, due to the blood-brain barrier, biomarkers from the brain wouldn’t be found in peripheral blood in sufficient quantities to deliver a diagnosis. But analytical techniques have advanced in sensitivity in recent years, allowing small amounts of biomarkers in the blood to be detected.
The C2N test relies on the ratio of two isoforms of the amyloid-β protein, Aβ42 and Aβ40, that aggregate to form amyloid plaques in the brain, combined with the presence of isoforms of apolipoprotein E (ApoE) that reflect whether the patient caries a genetic variant associated with Alzheimer’s risk. The results are combined into a score that indicates the probability that a patient would be found to have amyloid plaques if they were to undergo an amyloid PET scan. Doctors can then consider the test results along with other information about the patient to arrive at a diagnosis. According to data posted on the company’s website, a study in 686 patients with cognitive impairment found that those with scores above a certain cutoff point had a positive amyloid PET scan 92 percent of the time, while those with scores below a certain cutoff had a 77 percent chance of having a negative result on the PET scan.
While no drugs have yet been approved to treat Alzheimer’s, being able to distinguish it from other possible causes of cognitive impairment is nonetheless valuable, Fillit and Schindler say. As a clinician, Schindler says, “I want to know what my patients have.” That can be complicated because in many cases, “they don’t just have memory impairment, they’re taking multiple medications, they have all sorts of health issues,” she says. “And sometimes it’s really hard to know whether the symptoms they’re experiencing are due to something like Alzheimer’s or something else.”
Symptom-based diagnosis of Alzheimer’s disease is only about 70 percent accurate, notes Colin Masters of the Florey Institute of Neuroscience and Mental Health in Australia who was part of the team that first characterized the amyloid plaques in the disease. If a clinician suspects the disease but the blood test returns a negative result, this “will force the clinicians to go and look harder for other causes of dementia,” says Masters, who collaborates with one of the test’s developers but has no ties to C2N. He adds that once an amyloid-targeting Alzheimer’s drug is approved, the test will be useful in determining who should receive it. Such a treatment may not be far off: the Biogen drug candidate aducanumab is set for review by a US Food and Drug Administration panel later this week.
The blood test is also likely to be a boon for clinical trials to develop other drugs, as it will make it easier to screen patients for recruitment, Fillit says. “Screening and enrollment represents up to fifty percent of the cost of clinical trials in Alzheimer’s disease, and one Phase 3 trial costs three to four hundred million dollars,” he says, calling the blood test a “huge advance in clinical trials.”
Clarification (November 2): This article has been amended to state Masters’s working relationship with one of the test’s developers.