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.
Anatomic pathologists understand that, along with breast cancer, diagnostic testing for prostate cancer accounts for a high volume of clinical laboratory tests. Thus, a recent study indicating that a new artificial intelligence (AI)-based software tool can dramatically improve physicians’ ability to identify the extent of these cancers will be of interest.
“The study found that Unfold AI’s patient-specific encapsulation confidence score (ECS), which is generated based on multiple patient data points, including MRI scans, biopsy results, PSA [prostate-specific antigen] data, and Gleason scores, is critical for predicting treatment success,” an Avenda press release states. “These findings emphasize the importance of Unfold AI’s assessment of tumor margins in predicting treatment outcomes, surpassing the predictive capability of conventional parameters.”
“Unfold AI’s ability to identify tumor margins and provide the ECS will improve treatment recommendations and allow for less-invasive interventions,” said study co-author Wayne Brisbane, MD, a urologic oncologist and UCLA medical professor, in another press release. “This more comprehensive approach enhances our ability to predict treatment outcomes and tailor interventions effectively to individual patient needs.”
“This study is important because it shows the ability of AI to not only replicate expert physicians, but to go beyond human ability,” said study co-author Wayne Brisbane, MD (above), a urologic oncologist and UCLA medical professor, in a press release. “By increasing the accuracy of cancer identification in the prostate, more precise and effective treatment methods can be prescribed for patients.” Clinical laboratories that work with anatomic pathologists to diagnose prostate and other cancers may soon have a new AI testing tool. (Photo copyright: UCLA.)
How Unfold AI Works
To gauge the extent of prostate tumors, surgeons typically evaluate results from multiple diagnostic methods such as PSA tests and imaging scans such as MRIs, according to a UCLA press release. However some portions of a tumor may be invisible to an MRI, causing doctors to underestimate the size.
Unfold AI, originally known as iQuest, was designed to analyze data from PSA, MRI, fusion biopsy, and pathology testing, according to a company brochure. From there, it generates a 3D map of the cancer. Avenda’s website says the technology provides a more accurate representation of the tumor’s extent than conventional methods.
“Accurately determining the extent of prostate cancer is crucial for treatment planning, as different stages may require different approaches such as active surveillance, surgery, focal therapy, radiation therapy, hormone therapy, chemotherapy, or a combination of these treatments,” Brisbane said in the UCLA press release.
Putting AI to the Test
In the new study, the UCLA researchers enlisted seven urologists and three radiologists to review 50 prostate cancer cases. Each patient had undergone prostatectomy—surgical removal of all or part of the prostate—but might have been eligible for focal therapy, a less-aggressive approach that uses heat, cryotherapy, or electric shocks to attack cancer cells more selectively.
The physicians came from five hospitals and had a wide range of clinical experience from two to 23 years, the researchers noted in The Journal of Urology.
They reviewed clinical data and examined MRI scans of each patient, then “manually drew outlines around the suspected cancerous areas, aiming to encapsulate all significant disease,” the press release states. “Then, after waiting for at least four weeks, they reexamined the same cases, this time using AI software to assist them in identifying the cancerous areas.”
The researchers analyzed the physicians’ work, evaluating the accuracy of the cancer margins and the “negative margin rate,” indicating whether the clinicians had identified all of the cancerous tissue. Using conventional approaches, “doctors only achieved a negative margin 1.6% of the time,” the press release states. “When assisted by AI the number increased to 72.8%.”
The clinicians’ accuracy was 84.7% when assisted by AI versus 67.2% to 75.9% for conventional techniques.
They also found that clinicians who used the AI software were more likely to recommend focal therapy over more aggressive forms of treatment.
“We saw the use of AI assistance made doctors both more accurate and more consistent, meaning doctors tended to agree more when using AI assistance,” said Avenda Health co-founder and CEO Shyam Natarajan, PhD, who was senior author of the study.
“These results demonstrate a marked change in how physicians will be able to diagnose and recommend treatment for prostate cancer patients,” said Natarajan in a company press release. “By increasing the confidence in which we can predict a tumor’s margins, patients and their doctors will have increased certainty that their entire tumor is treated and with the appropriate intervention in correlation to the severity of their case.”
UCLA’s study found that AI can outperform doctors both in sensitivity (a higher detection rate of positive cancers) and specificity (correctly detecting the sample as negative). That’s relevant and worth watching for further developments.
Pathologists and clinical laboratory managers should consider this use of AI as one more example of how artificial intelligence can be incorporated into diagnostic tests in ways that allow medical laboratory professionals to diagnose disease earlier and more accurately. This will improve patient care because early intervention for most diseases leads to better outcomes.
