Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio test measures blood biomarkers associated with the disease
Clinical laboratories could soon find themselves playing a significant role in Alzheimer’s care as the US Food and Drug Administration (FDA) announced its first-ever clearance of a blood test to assist in diagnosing the cognitive disease.
The agency issued a 510(k) clearance for the Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio test from Fujirebio Diagnostics, Inc. The test is intended for “the early detection of amyloid plaques associated with Alzheimer’s disease in adult patients, aged 55 years and older, exhibiting signs and symptoms of the disease,” according to an FDA press release.
“Nearly seven million Americans are living with Alzheimer’s disease, and this number is projected to rise to nearly 13 million,” said FDA Center for Devices and Radiological Health Director Michelle Tarver, MD, PhD, in the press release. “Today’s clearance is an important step for Alzheimer’s disease diagnosis, making it easier and potentially more accessible for US patients earlier in the disease.”
“Alzheimer’s disease impacts too many people, more than breast cancer and prostate cancer combined,” said FDA Commissioner Martin A. Makary, MD, MPH, in the FDA press release.
“Knowing that 10% of people aged 65 and older have Alzheimer’s, and that by 2050 that number is expected to double, I am hopeful that new medical products such as this one will help patients,” said FDA Commissioner Martin A. Makary, MD, MPH, in the FDA press release. (Photo copyright: Johns Hopkins University.)
Blood Protein Test Details
Fujirebio’s test calculates the ratio of two blood proteins, pTau217 and β-amyloid 1-42. “This ratio is correlated to the presence or absence of amyloid plaques in the patient’s brain, reducing the need for a PET scan,” the press release states.
The FDA said it has already authorized or cleared similar tests that use cerebrospinal fluid (CSF) samples obtained through an invasive spinal tap. “This new Lumipulse test only requires a simple blood draw, making it less invasive and much easier for patients to access,” the FDA said.
In granting the clearance, the agency looked at data from a clinical study of 499 adults displaying signs of cognitive impairment. Close to 92% of participants with positive test results had amyloid plaques as determined by amyloid PET scan or CSF test results. Approximately 97% with negative results from the Lumipulse test were also shown to be negative in the PET scan or CSF test. Fewer than 20% of the patients received indeterminate results, which would require additional testing.
The primary risks of the test are false positive or false negative results, the federal agency noted.
“Importantly, the Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio is not intended as a screening or stand-alone diagnostic test and other clinical evaluations or additional tests should be used for determining treatment options,” the FDA said.
‘Wild West’ Marketplace
In their reporting of this story,MedPage Today and the Associated Press both noted that some laboratory-developed tests can already measure plasma biomarkers associated with Alzheimer’s.
“But those tests aren’t reviewed by the FDA and generally aren’t covered by insurance,” the AP reported. “Doctors have also had little data to judge which tests are reliable and accurate, leading to an unregulated marketplace that some have called a ‘wild west.’”
Neurologist Richard S. Isaacson, MD, told CNN that he’s already using the test for research purposes. “It can provide better clarity into whether a person experiencing memory loss may have Alzheimer’s disease,” he said.
However, he cautioned that more research is needed to allow doctors to make best use of the test.
“I think the next step as a field is, we need to advance education about what these tests mean and what they don’t and who they should be used for,” he told CNN. “Because they mean different things in different people depending on their risk factors and whether they have symptoms. So, we’re still early.”
“The results must be interpreted in conjunction with other patient clinical information,” the FDA acknowledged in their press release.
Other Alzheimer’s Tests
The FDA said it reviewed the Lumipulse test through the 510(k) premarket notification pathway, in which the federal agency determines if a device is “substantially equivalent to a legally marketed predicate device.”
In this case, the agency found that the test is substantially equivalent to Fujirebio’s Lumipulse G β-amyloid Ratio (1-42/1-40), which measures the same proteins in CSF samples. The FDA authorized that device in 2022, according to a Fujirebio press release. That test uses Fujirebio’s automated Lumipulse G1200 instrument system.
Other companies including Roche, Eli Lilly, and C2N Diagnostics are also developing Alzheimer’s tests they intend to submit for FDA review, the AP reported.
Already-existing clinical laboratory blood test may be new standard for detecting Alzheimer’s biomarkers
In Sweden, an independent study of an existing blood test for Alzheimer’s disease—called ALZpath—determined that this diagnostic assay appears to be “just as good as, if not surpass, lumbar punctures and expensive brain scans at detecting signs of Alzheimer’s in the brain,” according to a report published by The Guardian.
Alzheimer’s disease is one of the worst forms of dementia and it affects more than six million people annually according to the Alzheimer’s Association. Clinical laboratory testing to diagnose the illness traditionally involves painful, invasive spinal taps and brain scans. For that reason, researchers from the University of Gothenburg in Sweden wanted to evaluate the performance of the ALZpath test when compared to these other diagnostic procedures.
Motivated to seek a less costly, less painful, Alzheimer’s biomarker for clinical laboratory testing, neuroscientist Nicholas Ashton, PhD, Assistant Professor of Neurochemistry at the University of Gothenburg, led a team of scientists that looked at other common biomarkers used to identify changes in the brain of Alzheimer’s patients. That led them to tau protein-based blood tests and specifically to the ALZpath blood test for Alzheimer’s disease developed by ALZpath, Inc., of Carlsbad, Calif.
In their JAMA article, they wrote, “the pTau217 immunoassay showed similar accuracies to cerebrospinal fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies.”
In an earlier article published in medRxiv, Ashton et al wrote, “Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer’s disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited.”
Thus, the discovery of an existing pTau217 assay (ALZpath) that is accessible and affordable is a boon to Alzheimer’s patients and to the doctors who treat them.
“The ALZpath pTau217 assay showed high diagnostic accuracy in identifying elevated amyloid (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau (AUC, 0.93-0.97; 95%CI 0.84-0.99) in the brain across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and equivalent to CSF [cerebrospinal fluid] biomarkers,” an ALZpath press release noted.
“This is an instrumental finding in blood-based biomarkers for Alzheimer’s, paving the way for the clinical use of the ALZpath pTau217 assay,” stated Henrik Zetterberg, MD, PhD (above), Professor of Neurochemistry at the University of Gothenburg and co-author of the study. “This robust assay is already used in multiple labs around the globe.” Clinical laboratories may soon be receiving doctors’ orders for pTau217 blood tests for Alzheimer’s patients. (Photo copyright: University of Gothenburg.)
Study Details
Ashton’s team conducted a cohort study that “examined data from three single-center observational cohorts.” The cohorts included:
“Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023,” the researchers wrote.
These trials from the US, Canada, and Spain featured 786 participants and featured “either a lumbar puncture or an amyloid PET scan to identify signs of amyloid and tau proteins—hallmarks of Alzheimer’s disease,” The Guardian reported, adding that results of the University of Gothenburg’s study showed that the ALZpath pTau217 blood test “was superior to brain atrophy assessments, in identifying signs of Alzheimer’s.”
“80% of individuals could be definitively diagnosed on a blood test without any other investigation,” Ashton told The Guardian.
Diagnosis Needed to Receive Alzheimer’s Disease Treatments
“If you’re going to receive [the new drugs], you need to prove that you have amyloid in the brain,” Ashton told The Guardian. “It’s just impossible to do spinal taps and brain scans on everyone that would need it worldwide. So, this is where the blood test [has] a huge potential.”
Even countries where such drugs were not yet available (like the UK) would benefit, Ashton said, because the test, “Could potentially say that this is not Alzheimer’s disease and it could be another type of dementia, which would help to direct the patient’s management and treatment routine.”
However, Ashton himself noted the limitations of the new findings—specifically that there is no success shown yet in Alzheimer’s drugs being taken by symptom-free individuals.
“If you do have amyloid in the brain at 50 years of age, the blood test will be positive,” he said. “But what we recommend, and what the guidelines recommend with these blood tests, is that these are to help clinicians—so someone must have had some objective concern that they have Alzheimer’s disease, or [that] their memory is declining,” he told The Guardian.
Experts on the Study Findings
“Blood tests could be used to screen everyone over 50-years old every few years, in much the same way as they are now screened for high cholesterol,” David Curtis, MD, PhD, Honorary Professor in the Genetics, Evolution and Environment department at University College London, told The Guardian.
“Results from these tests could be clear enough to not require further follow-up investigations for some people living with Alzheimer’s disease, which could speed up the diagnosis pathway significantly in future,” Richard Oakley, PhD, Associate Director of Research and Innovation at the Alzheimer’s Society, UK, told The Guardian.
Though Oakley found the findings promising, he pointed out what should come next. “We still need to see more research across different communities to understand how effective these blood tests are across everyone who lives with Alzheimer’s disease,” he said.
“Expanding access to this highly accurate Alzheimer’s disease biomarker is crucial for wider evaluation and implementation of AD blood tests,” the researchers wrote in JAMA Neurology.
“ALZpath makers are in discussions with labs in the UK to launch it for clinical use this year, and one of the co-authors, Henrik Zetterberg, MD, PhD, Professor of Neurochemistry at the University of Gothenburg, is making the assay available for research use as part of the ‘biomarker factory’ at UCL,” The Guardian reported.
In the US, to be prescribed any of the available Alzheimer’s medications, a doctor must diagnose that the patient has amyloid in the brain. A pTau217 diagnostic blood test could be used to make such a diagnosis. Currently, however, the test is only available “for research studies through select partner labs,” Time reported.
“But later this month, doctors in the US will be able to order the test for use with patients. (Some laboratory-developed tests performed by certain certified labs don’t require clearance from the US Food and Drug Administration.),” Time added.
It may be that the University of Gothenburg study will encourage Alzheimer’s doctors in the UK and around the world to consider ordering pTau217 diagnostic blood tests from clinical laboratories, rather than prescribing spinal taps and brains scans for their Alzheimer’s patients.
