By Diagnostics World Staff
July 29, 2024 | A study published in JAMA yesterday suggests blood tests can more accurately detect Alzheimer’s disease than physicians, and points to a way forward for more extensive Alzheimer’s testing. More blood testing developments are on display at this week's Alzheimer’s Association International Conference.
The JAMA research, conducted in Sweden, comprised a cohort was made of 1213 patients, with an average age of 74.2 years. Slightly less than half were women (48%) and all had some noted cognitive decline: 23% had subjective cognitive decline, 44% had mild cognitive impairment, and 33% had dementia. Half of the patients had AD pathology. (DOI: 10.1001/jama.2024.13855)
The researchers compared two biomarkers associated with Alzheimer’s Disease—tau and amyloid-β—in a commercial blood test, looked at how that test fared when analyzed biweekly, and compared the biomarker test to physicians’ diagnostic accuracy.
The researchers began with the ratio of phosphorylated tau217 (p-tau217) to non–p-tau217 (expressed as percentage of p-tau217)—a test previously shown to provide comparable diagnostic accuracy (90%) to clinically-approved cerebrospinal fluid biomarker tests. They sought to improve diagnostic accuracy by combining those findings with the amyloid-β 42 and amyloid-β 40 (Aβ42:Aβ40) plasma ratio. The combined score—the amyloid probability score 2 (APS2)—is offered by C2N Diagnostics via the PrecivityAD2 test.
Physician Accuracy
The researchers asked primary care physicians and dementia specialists whether they thought their patients had Alzheimer disease pathology based on clinical examination, cognitive testing, and a computed tomographic scan—but before seeing any Alzheimer disease biomarker results.
Researchers found that dementia specialists did a bit better than primary care physicians. They had an overall diagnostic accuracy of 71%, and their average certainty assessment was a score of 6 on a scale from 0 (very low) to 10 (very high) for the level of diagnostic confidence. Primary care physicians scored lower, with an overall diagnostic accuracy of 58% and a certainty assessment of 5.8.
Next Steps
The researchers highlighted limitations in the scope of work, primarily in geography of the patient population, and called for further research to simulate use of the tests in a clinical environment.
The higher diagnostic accuracy of the blood test indicates that it could be suitable for implementation in primary care, the authors write in the paper, though they note that further studies should examine its effect on clinical care. “In addition to improving diagnostic accuracy, a positive test result could further support the initiation of widely available treatments (such as cholinesterase inhibitors). Even more importantly, it could aid in identifying potential candidates for timely anti-amyloid treatment and who should be referred to secondary care,” they continue.
Because these blood tests have accuracy on par with cerebrospinal fluid biomarkers—though they are more time-effective, cost-effective, and convenient for patients—the authors suggest that blood tests could replace cerebrospinal fluid tests.
The authors caution that the high diagnostic accuracy rates for the tests does not recommend using the blood-based tests in isolation. “It is crucial to emphasize that a biomarker for Alzheimer disease pathology, however accurate, should not serve as a standalone diagnostic test for Alzheimer disease but must be interpreted in a clinical context,” the authors write. “This is important because Alzheimer disease pathology can be asymptomatic for many years, and cognitive symptoms in some patients with Alzheimer disease pathology can be primarily caused by other conditions.”
Other Biomarker Updates
The Swedish researchers are not the only ones exploring blood-based biomarkers for Alzheimer’s Disease. At this week’s Alzheimer’s Association International Conference (AAIC), several groups are presenting work exploring this area.
Today, Quanterix Corporation presents new data at the event supporting a novel multi-marker approach to test for Alzheimer’s disease (AAIC poster 95706). p-Tau217 tests with a two-cutoff approach maximizes the accuracy of a p-Tau 217 test. This is the same strategy the Swedish researchers used. But the approach leaves a zone of intermediate risk between the two cutoffs representing inconclusive borderline amyloid status.
Quanterix investigated whether interrogating intermediate samples with a panel of additional Alzheimer’s-associated plasma biomarkers, including combinations of amyloid β 42, amyloid β 40, GFAP, and NfL, together with p-Tau217 in an algorithm that provides a single risk score, would improve the amyloid classification of uncertain results compared to a stand-alone p-Tau217 test. The research found that this multi-marker approach enabled accurate amyloid classifications for 151 of 228 previously uncertain results across a large, high-diversity cohort of symptomatic individuals, reducing the intermediate zone 3-fold from 31.2% to 10.5% compared to p-Tau 217 alone.
“With these novel multi-marker results, we are leveraging the best of our [LucentAD p-Tau 217] test along with other AD-relevant biomarkers,” said Masoud Toloue, CEO of Quanterix in a press relese. “We believe that a multi-marker approach is the next phase in the evolution of blood-based testing, not only for identifying and staging Alzheimer’s pathology, but also for informing important differential treatment pathways that include non-Alzheimer’s neurodegenerative diseases. The latter is an important consideration given approximately 30% of Alzheimer’s patients have pathologies other than AD.”
Tomorrow, Sunbird Bio will be presenting new data demonstrating that the company’s blood-biomarker tau signatures have the potential to accurately detect tau protein aggregation in the brain from a blood draw (AAIC poster 88533). The company believes the results suggest the technology could provide blood-based Alzheimer’s disease diagnosis equivalent to the gold-standard PET imaging.
“Our research continues to reveal the power of [extracellular vesicle]-bound proteins to serve as accurate biomarkers in the detection of neurological disorders, and the data we are presenting at AAIC underscore the promising potential of our blood-based diagnostic to directly detect Alzheimer’s disease via these particular tau proteins,” said John McDonough, executive chairman and CEO of Sunbird Bio, in a press release. “With a correlation of 92% to the gold standard PET scan, these data provide further evidence that our proprietary approach may deliver a diagnostic that improves patient outcomes in Alzheimer’s disease and other neurological disorders. We will continue to evaluate this platform, which could provide researchers and physicians with unparalleled insights not readily available from current tests.”