New recommendations from the Alzheimer’s Association call for Alzheimer’s blood tests to reach at least 90% sensitivity and specificity to be used in place of established diagnostic tools.
Alzheimer’s blood tests need to offer at least 90% sensitivity and 90% specificity before they can replace brain scans and spinal taps in diagnosis of the neurodegenerative disease, according to a new clinical practice guideline recommendation from the Alzheimer’s Association.
The health organization cautioned in a news release that “many commercially available blood-based biomarker tests do not meet these thresholds” for substituting amyloid PET imaging and cerebrospinal fluid (CSF) tests in Alzheimer’s diagnosis.
“The whole purpose of developing the clinical practice guideline is to try to create pragmatic recommendations for clinicians on how to choose the right test for the right patient at the right time,” Rebecca Edelmayer, PhD, Alzheimer’s Association Vice President of Scientific Engagement, told Medscape. “The blood- based biomarker area is still a burgeoning field,” added Edelmayer, a guideline Co-author.
Clinical laboratories may find the recommendations useful in making decisions about additions to lab test menus and in educating clinicians on appropriate test ordering.
“Pathologically, Alzheimer’s disease is defined by the accumulation of extracellular cortical plaques composed of amyloid-beta fibrils and intracellular neurofibrillary tangles containing abnormal hyperphosphorylated tau protein. These pathologies manifest many years or even decades before the onset of clinical symptoms,” the authors wrote.
Compared to “standard-of-care” amyloid PET imaging and CSF tests, blood-based biomarkers may cost less and reduce patients’ stress, the Alzheimer’s Association pointed out, adding that blood tests are not a replacement for clinical evaluations by healthcare providers.
“What we’ve learned from all of the evidence so far is that some of these biomarkers, like tau217, tend to be very accurate predictors of Alzheimer’s disease biology in the brain, and they can be used to aid in the diagnostic process early on—sometimes even before tau tangle formations can be visualized with brain imaging,” Rebecca Edelmayer, PhD, Alzheimer’s Association Vice President of Scientific Engagement, said in the Medscape article. (Photo credit: Alzheimer’s Association.)
Panel Reviews Phosphorylated-tau and Amyloid-beta
To discover the diagnostic accuracy of blood-based biomarkers in Alzheimer’s disease, a panel of 11 clinicians, convened by the Alzheimer’s Association, did a systematic review using this methodology described in the association’s statement:
Reviewed 49 observational studies and assessed 31 tests.
Focused on blood-based biomarkers including plasma phosphorylated-tau (p-tau) and amyloid beta (Aβ) tests measuring: p-tau217, ratio of p-tau217 to non-p-tau217 x 100, p-tau181, p-tau231, and ratio of Aβ42 to Aβ40.
Panelists, unaware of the tests they were reviewing, did not rank or endorse tests.
Diagnostic accuracy varied among the assays with sensitivity ranging from 49.31% to 91.41% and specificity from 61.54% to 96.72%, Neurology Advisorreported.
Tests evaluated included these, which were also recently reported on by Dark Daily:
Based on the systematic review, the panel released the following recommendations for use of blood-based biomarker tests when Alzheimer’s disease is suspected, according to the Alzheimer’s Association:
Tests with 90% sensitivity and 90% specificity or more may stand-in for PET amyloid imaging or CSF Alzheimer’s biomarker testing.
Tests with at least 90% sensitivity and 75% specificity can serve as triaging assays whereby negative results rule out Alzheimer’s “with high probability” while positive findings need confirmation with PET or CSF testing.
“For the first time, we have a rigorously evidence-based guideline that empowers clinicians to use blood biomarker tests confidently and consistently. Adoption of these recommendations will lead to quicker, more accessible, more accurate diagnoses, and better outcomes,” said Maria Carillo, PhD, Alzheimer’s Association Chief Science Officer and Medical Affairs Lead and a Co-author of the guideline.
The guideline is part of the Alzheimer’s Association resources to promote best practices. It plans development of other reports about cognitive assessment tools, clinical implementation of staging, and Alzheimer’s prevention.
The trade association is publicly promoting the benefits of biomarker testing and AI’s benefits to diagnostics
One of the core tenets to getting federal lawmaker support for business is to tell them what an industry does. In that vein, the American Clinical Laboratory Association (ACLA) has released a new promotion that highlights applications of companion diagnostics, rapid whole genome sequencing, drug screening, biomarker testing, and infectious disease management.
One of the end goals? To sway Congress to take action against proposed reimbursement cuts to clinical lab test rates.
The ACLA campaign, known as the “Power of Knowing,” took center stage during a panel discussion at the ACLA Annual Meeting, held Feb. 27 in Washington, DC. One objective, panelists said, is to draw attention to the profession’s role in prevention and early detection of diseases, according to report from Medtech Insight.
“The association is working hard to demonstrate to policymakers the value of clinical laboratory testing through the Power of Knowing as they make policy decisions on reimbursement and clinical laboratory infrastructure that’s necessary for robust patient access to these innovative diagnostics,” said panel moderator Elyse Oveson, according to Medtech Insight. Oveson serves as ACLA chief of advocacy operations.
In March 2024, ACLA released digital ads urging Congress to pass the Saving Access to Laboratory Services Act (SALSA), which would have prevented a 15% cut in Medicare reimbursement for approximately 800 laboratory tests.
“A sustainable reform of the Medicare payment system for clinical laboratory services is vital to protect and enhance patient care, foster innovation, and ensure the stability of clinical laboratories nationwide,” ACLA president Susan Van Meter said at the time.
“If patients don’t have their biomarkers profiled for them at diagnosis and again at progression, there’s a very real chance that they would be put on the incorrect therapy that could lead to them having real harm in their health. So, we view biomarkers as critical,” said Nikki Martin (above), senior director of precision medicine initiatives for the LUNGevity Foundation, during the 2025 ACLA Annual Meeting. (Photo copyright: LinkedIn.)
Martin told attendees that biomarker tests should be part of the standard of care in lung cancer diagnosis, Medtech Insight reported. These tests analyze blood or other patient samples to identify molecules associated with specific diseases.
“For patients with non-small cell lung cancer, biomarkers are everything,” said Martin during the panel discussion. Many patients with advanced metastatic cancer, she said, “are not receiving comprehensive biomarker testing, and if they’re not, then they’re at risk of having much worse outcomes.”
Edelmayer discussed progress in developing biomarker tests for early diagnosis of Alzheimer’s disease. “The momentum is palpable among the research community,” she said. “We’re now starting to see the shift into implementation and more types of tools and technologies being available to clinicians to help patients.”
However, Edelmayer acknowledged that progress in developing Alzheimer’s tests and treatments has been slow.
“There’s never going to be a single test to help diagnose Alzheimer’s disease,” she said. “We recognize that it’s going to be a combination approach.”
New Video Campaign
The campaign’s latest advertising is summed up in a 90-second sizzle reel in which clinical laboratory leaders discuss various ways in which the profession supports healthcare.
One theme in the video is the growing use of artificial intelligence (AI) in the profession. “AI-enabled diagnostics are tools that use machine learning to analyze vast amounts of data from patient records to genomic profiles,” said Kate Sasser, PhD, chief scientific officer of Tempus, in the video. “These systems can recognize patterns in the data that humans may not easily see and help clinicians detect diseases earlier and more accurately.”
“By harnessing these cutting-edge tools, we can move closer to a world where treatments are no longer one size fits all but are instead tailored to the unique genetic and molecular profile of each patient,” said Elias Zerhouni, MD, president and vice chairman of OPKO Health, in a recent video produced as part of the ACLA’s Power of Knowing campaign.
The campaign website includes additional videos as well as downloadable graphics that can be shared on social media.
As new diagnostic assays are cleared by regulators, clinical laboratories will play a key role in identifying appropriate patients for new less-invasive Alzheimer’s tests
With multiple companies racing to develop a blood-based test for Alzheimer’s disease (AD), clinical laboratories may soon have new less-invasive diagnostic assays for AD on their menus.
Why a race? Because a less-invasive clinical laboratory test that uses a venous blood draw (as opposed to a spinal tap)—and which has increased sensitivity/specificity—has a potentially large market given the substantial numbers of elderly predicted to develop Alzheimer’s over the next decade. It has the potential to be a high volume, high dollar diagnostic test.
In fact, Mordor Intelligence estimates that the market for Alzheimer’s disease therapeutics will grow from $7.7 billion in 2024 to $10.10 billion by 2029.
Alzheimers.gov, an official website of the US government, says, “Researchers have made significant progress in developing, testing, and validating biomarkers that detect signs of the disease process. For example, in addition to PET scans that detect abnormal beta-amyloid plaques and tau tangles [abnormal forms of tau protein] in the brain, NIH-supported scientists have developed the first commercial blood test for Alzheimer’s. This test and others in development can not only help support diagnosis but also be used to screen volunteers for research studies.”
Additionally, the US Food and Drug Administration (FDA) is clearing new Alzheimer’s drugs for clinical use. The pharma companies behind these drugs need clinical laboratory tests that accurately diagnosis the disease and confirm that it would be appropriate for the patient to receive the new therapeutic drugs, a key element of precision medicine.
“The big promise for blood tests is that they will eventually be accessible, hopefully, cost-effective, and noninvasive,” Rebecca Edelmayer, PhD (above), Vice President, Scientific Engagement, Alzheimer’s Association, told USA Today. “The field is really moving forward with use of these types of tests,” she added. Clinical laboratories may soon have these new assays on their test menus. (Photo copyright: Alzheimer’s Association.)
Companies in the Race to Develop Blood-based Alzheimer’s Tests
Researchers found that C2N’s blood test can detect brain amyloid status with “sensitivity, specificity, positive and negative predictive values that approximate those of amyloid positron emission tomography (PET) imaging,” according to a news release.
“The PrecivityAD2 blood test is intended for use in patients aged 55 and older with signs or symptoms of mild cognitive impairment or dementia who are undergoing evaluation of Alzheimer’s disease or dementia. Only a healthcare provider can order the PrecivityAD2 test,” the news release noted.
“The PrecivityAD2 blood test showed strong clinical validity with excellent agreement with brain amyloidosis by PET,” the researchers wrote.
The PrecivityAD2 test, which is mailed directly by C2N to doctors and researchers, is performed at the company’s CLIA-certified lab, according to USA Today, which added that the cost of $1,450 is generally not covered by insurance plans.
Expanding Test Access with IVD Companies
ALZpath, Inc. has a different approach to the Alzheimer’s disease test market. The Carlsbad, Calif.-based company, set up an agreement with in vitro diagnostics (IVD) company Roche Diagnostics for use of its phosphorylated tau (pTau)217 antibody “to develop and commercialize an Alzheimer’s disease diagnostic blood test that will be offered on the Roche Elecsys platform,” according to a news release.
Roche received FDA breakthrough device designation on the Elecsys pTau217 test earlier this year and will work with pharmaceutical company Eli Lilly to commercialize the test.
Estimates show 75% of dementia cases go undetected—a number which could grow to 140 million by 2050, according to data shared by Roche with Fierce Biotech.
“We plan to leverage our installed base of diagnostic systems, which is the largest in the world, to ensure we are able to create access to this test for those who need it the most,” Matt Sause, CEO, Roche Diagnostics, told Fierce Biotech.
Another IVD company, Beckman Coulter, recently signed an agreement to use ALZpath’s pTau217 antibody test in its DxI 9000 Immunoassay Analyzer. In a news release, Kathleen Orland, SVP and General Manager of the Clinical Chemistry Immunoassay Business Unit at Beckman Coulter, said that the test had “high performance in detecting amyloid pathology” and could “integrate into our advanced DxI 9000 platform to support broad-based testing.”
Clinical Laboratory Participation
The FDA is drafting new guidance titled, “Early Alzheimer’s Disease: Developing Drugs for Treatment” that is “intended to assist sponsors in the clinical development of drugs for the treatment of the stages of sporadic Alzheimer’s disease (AD) that occur before the onset of overt dementia.”
Pharma companies intent on launching new drugs for Alzheimer’s will need medical laboratory tests that accurately diagnosis the disease to confirm the medications would be appropriate for specific patients.
Given development of the aforementioned pTau217 antibody tests, and others featuring different diagnostic technologies, it’s likely clinical laboratories will soon be performing new assays for diagnosing Alzheimer’s disease.
