麻豆传媒

PHILADELPHIA -- A blood test performed better than a standard evaluation by primary care doctors or dementia specialists in detecting Alzheimer's disease among people with cognitive symptoms.

The PrecivityAD2 blood test algorithm -- which produced an outcome called the amyloid probability score 2 (APS2) -- had a diagnostic accuracy of 91%, compared with 61% diagnostic accuracy after standard clinical evaluations by primary care physicians, and 73% accuracy after evaluations by dementia specialists.

The APS2 incorporates the ratio of plasma phosphorylated tau 217 (p-tau217) relative to non-p-tau217, combined with an amyloid-beta 42/amyloid-beta 40 plasma ratio, based on mass spectrometry assays. Its accuracy was compared with physician diagnoses based on standard evaluations that included clinical exams, cognitive tests, and a CT scan.

The findings, presented at the Alzheimer's Association International Conference by Oskar Hansson, MD, PhD, of Skåne University Hospital in Malmö, Sweden, were published simultaneously in .

"It's very difficult to accurately diagnose Alzheimer's disease without the support of accurate biomarkers," co-author Sebastian Palmqvist, MD, PhD, also of Skåne University Hospital told 麻豆传媒. "About 25% to 30% of patients with cognitive impairment at specialist clinics are misdiagnosed when biomarkers are not used, and the frequency of misdiagnosis in primary care is likely even higher," he said.

"We think this blood test can substantially improve the diagnostic work-up of Alzheimer's disease in specialist clinics without good access to CSF [cerebrospinal fluid] or PET tests for Alzheimer's disease," Palmqvist continued. "In clinics with access to CSF or PET, the blood test can likely replace those diagnostic methods in many patients."

Blood tests -- once they're confirmed to be more than 90% accurate and become more widely available -- can possibly redefine the diagnostic work-up for Alzheimer's, noted Maria Carrillo, PhD, chief science officer of the Alzheimer's Association.

"While, at this time, doctors in primary and secondary care should use a combination of cognitive and blood or other biomarker testing to diagnose Alzheimer's, blood tests have the potential to increase the accuracy of early diagnoses and maximize the opportunity to access Alzheimer's treatments as early as possible for better outcomes," Carillo said.

The tests should be used only on patients with cognitive symptoms, the Alzheimer's Association maintained. Testing cognitively unimpaired individuals outside of research studies is not recommended according to the 2024 criteria for diagnosing Alzheimer's disease. In 2022, the Alzheimer's Association also published for blood biomarkers.

"We personally recommend testing only patients with cognitive impairment and not the 'worried well,'" Palmqvist said. "Education of clinicians who will use the tests is needed, so they test the correct patients, and they know how to interpret the results."

The study assessed 1,213 patients in the Swedish and studies who had clinical evaluations due to cognitive symptoms from February 2020 through January 2024. Mean age was about 74 and 48% were women; 23% had subjective cognitive decline, 44% had mild cognitive impairment, and 33% had dementia. In both the primary care and secondary care assessments, 50% of patients had Alzheimer's pathology.

One plasma sample from each patient was analyzed as part of a single batch for each cohort. The blood test also was evaluated prospectively in each cohort, with one plasma sample per patient sent for analysis within 2 weeks of collection.

The primary outcome was Alzheimer's pathology determined by abnormal CSF amyloid ratios and p-tau217, evaluated by calculating predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and area under the curve (AUC) values.

When plasma samples were analyzed in a single batch in the primary care cohort, the APS2 had an AUC of 0.97, PPV of 91%, and NPV of 92%. In the secondary care cohort, AUC was 0.96, PPV was 88%, and NPV was 87%.

When plasma samples were analyzed prospectively, the APS2 showed an AUC in the primary care cohort of 0.96, PPV of 88%, and NPV of 90%. In the secondary care cohort, AUC was 0.97, PPV was 91%, and NPV was 91%.

The APS2 showed high accuracy using pre-defined cutoff values, ranging from 88% to 92% across all four cohorts. In the overall population, the diagnostic accuracy of APS2 (90%, 95% CI 88%-92%) was the same as the diagnostic accuracy using the percentage of p-tau217 alone (90%, 95% CI 88%-91%).

The test in this study was performed at a single U.S. lab, noted Stephen Salloway, MD, MS, of Brown University in Providence, Rhode Island, and colleagues, in a accompanying the research paper.

"There are many other high-performing immunoassays for the amyloid and tau proteins that are in development and may become more widely available," they pointed out.

A key limitation of the Swedish study was its lack of racial and ethnic diversity, making it tough to generalize findings to other populations, Salloway and co-authors observed. In the U.S., Alzheimer's blood tests will need FDA approval and CMS coverage to become widely adopted, they added.

"Overall, this study marks a milestone in blood biomarker development, as a blood test for Alzheimer's disease moves from the research world to dementia specialists and now into the hands of primary care physicians," wrote Gil Rabinovici, MD, and Lawren VandeVrede, MD, PhD, both of the University of California San Francisco, in a editorial.

"It is truly humbling to reflect on the fact that verification of Alzheimer's disease pathology, once purely the purview of the neuropathologist, can now be accomplished in the primary care clinic."