The first direct-to-consumer Alzheimer’s disease blood test has arrived. Quest Diagnostics, a worldwide diagnostic service headquartered in Secaucus, New Jersey, announced on July 31 that it would market a plasma Aβ42/ Aβ40 Alzheimer’s test to the public.
- Quest Diagnostics is selling an AD blood test directly to consumers.
- No peer-reviewed data are published on the test.
- It has low specificity, potentially generating many false-positive results.
- Experts fear it will do more harm than good.
The “AD-Detect Test” is available on the Quest website for $399 to anyone over 18. After going in for a blood draw at a Quest clinic, purchasers will receive a digital report with the results, and be offered the chance to discuss them via telemedicine with an “independent physician.” The assay uses a mass-spectrometry methodology similar to blood tests developed at Washington University in St. Louis. Unlike those tests, however, there are no published data on how Quest's test performs, nor on how it was validated.
Alzheimer’s researchers contacted by Alzforum universally decried Quest's decision. In addition to concerns about the test’s accuracy, they stressed the need for blood tests to be interpreted by a knowledgeable dementia specialist. “This is clearly not a good idea," Philip Scheltens, who last month retired from VU University, Amsterdam, wrote to Alzforum. “Every diagnostic test should be used in the context of a proper workup led by a skilled clinician,” he added (comment below). Scheltens now heads EQT Life Sciences Dementia Fund.
Suzanne Schindler at WashU noted that people tend to trust blood tests, and likely will not understand the uncertainty and nuances of being amyloid-positive or -negative. “People will think they have a clear answer, when they do not,” Schindler told Alzforum. More broadly, lack of clear standards and regulations, combined with high demand, could lead to many poorly validated tests coming on the market.
Scientists have been working on AD blood tests for many years, and the topic took on new urgency after the Food and Drug Administration approved the amyloid immunotherapy lecanemab (Jul 2023 news). More than a dozen such tests are in development at different companies (Hampel et al., 2023). So far, none are FDA-approved.
However, diagnostic tests do not need FDA approval to be marketed to the public. They can clear a lower bar by becoming CLIA-approved, meaning the assay has good test-retest reproducibility. Quest's test cleared this hurdle, but Alzheimer’s researchers are troubled by the lack of information about it. The only publicly available data come from a poster at the 2022 AAIC. In a cohort of 209 people, the test was reported to have a sensitivity of 0.89, specificity of 0.71, and AUC of 0.82.
AD researchers said this is not good enough for a consumer test. Such a test should have greater than 90 percent sensitivity and specificity, said Oskar Hansson at Lund University, Sweden (comment below). Henrik Zetterberg at the University of Gothenburg, Sweden, cautioned that the range of Aβ ratios for amyloid-positive and -negative people overlap significantly. “A direct-to-consumer test has to be super robust and easy to interpret. This is not the case for the plasma Aβ42/Aβ40 ratio, irrespective of which assay is used. The test needs to be interpreted together with additional biomarkers,” he wrote.
For comparison, the company C2N Diagnostics also sells a CLIA-approved mass spec plasma test using the Aβ42/Aβ40 ratio, but their test has extensive development and validation data behind it, and the company is not marketing directly to consumers.
How well would Quest's AD-Detect Test work in practice? If it were used in a memory clinic population, where 60 percent of patients have amyloid plaques, it would misdiagnose 18 percent of them, Schindler said (Rabinovici et al., 2019). However, the test is likely to reach a broader population, including cognitively healthy people concerned about their cognition.
The company’s website suggests its use for “anyone with a family history of Alzheimer’s disease” who is over 50. In this population, where 20 percent of people have amyloid plaques, the test would misdiagnose a quarter of them, Schindler calculated based on a recent study (Jansen et al., 2022). In particular, only 43 percent of positive results would be true positives. Earlier this month, Quest's website had recommended women take the test regardless of age or family history, but as of August 30, that sentence was no longer there.
Such a large number of false-positive test results would hike demand for follow-up testing and services from memory clinics. This would likely overwhelm them, noted Dennis Selkoe at Brigham and Women’s Hospital, Boston (comment below).
In the absence of expert guidance, misleading results could be severely distressing. “In our clinic, we see people in person to discuss a life-changing diagnosis such as Alzheimer’s disease,” Andrew Budson at the VA Boston Healthcare System wrote to Alzforum. Budson thinks blood tests are the future but that little good will come of direct-to-consumer testing.
Scientists noted many downsides. For one, a cognitively healthy person with a positive test would not qualify for treatment with lecanemab, and insurance would likely not cover follow-up testing. For another, positive tests could discourage people from investigating other, treatable, causes for their cognitive problems, such as medication side effects or depression, said Michelle Mielke at Wake Forest University in Winston-Salem, North Carolina. Charlotte Teunissen at Amsterdam UMC fears that inaccurate results will lead people to lose faith in AD blood testing. Teunissen cited the Dutch saying, “Trust arrives on foot, but leaves on horseback.”
Mielke and Teunissen are among the world's leading AD fluid biomarker experts. Both are working closely together, with Schindler, Hansson, and many others, in an ongoing effort started by Kaj Blennow, Henrik Zetterberg, and Maria Carrillo in 2011 (Aug 2012 conference news). Called the Global Biomarker Standardization Consortium, aka GBSC, these scientists work to ensure that CSF and blood tests are being properly developed, validated, and fully certified by their respective country's clinical chemistry agencies, such that they can be robust and trustworthy once they enter prime time (e.g. Blennow Q&A; see also Further Reading below and GBSC webpage).
In 2022, the Alzheimer’s Association published appropriate-use recommendations for blood-based biomarkers. They suggest that, for the time being, these tests be used only in specialty clinics, with positive results confirmed by CSF or amyloid PET (Aug 2022 news). Ultimately, FDA approval will be needed to define a gold-standard test, Schindler said. She predicted that the longer this takes, the more chaotic the arena will become in the interim.—Madolyn Bowman Rogers
- FDA Grants Traditional Approval to Leqembi
- CSF Markers: Goodbye, Research Use Only; Hello, Clinical
- Why Bother With Round Robins on Blood Tests? Q&A with Kaj Blennow
- Alzheimer's Blood Tests Have Arrived; Road to Broad Use Still Stretches On
- Hampel H, Hu Y, Cummings J, Mattke S, Iwatsubo T, Nakamura A, Vellas B, O'Bryant S, Shaw LM, Cho M, Batrla R, Vergallo A, Blennow K, Dage J, Schindler SE. Blood-based biomarkers for Alzheimer's disease: Current state and future use in a transformed global healthcare landscape. Neuron. 2023 Sep 20;111(18):2781-2799. Epub 2023 Jun 8 PubMed.
- Rabinovici GD, Gatsonis C, Apgar C, Chaudhary K, Gareen I, Hanna L, Hendrix J, Hillner BE, Olson C, Lesman-Segev OH, Romanoff J, Siegel BA, Whitmer RA, Carrillo MC. Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia. JAMA. 2019 Apr 2;321(13):1286-1294. PubMed.
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