The Future is p-Tau – Anticipating Direct-to-Consumer Alzheimer’s Disease Blood Tests

Recent studies suggest blood levels of phosphorylated tau (p-Tau) isoforms can detect both the tau and amyloid pathologies that define Alzheimer’s disease (AD).¹ More research is needed to replicate these results in large, diverse cohorts and to quantify a p-Tau blood test’s ability to predict the onset of dementia. Nevertheless, we anticipate that the ability to receive diagnostic and prognostic information with the ease of a blood test will revolutionize research and care. We also anticipate that it will be the basis of a profitable direct-to-consumer (DTC) test, one that highlights significant ethical and social challenges of DTC testing and AD.

A regulatory framework and business model for consumer-initiated tests are in place to move p-Tau blood testing from the clinic into our homes. The U.S. Food and Drug Administration (FDA) generally reviews DTC tests for moderate to high risk medical purposes, and DTC laboratory tests are regulated at both the federal and state levels. Consumers can already order blood tests via companies like VaultHealth, which sends providers to consumers’ homes to draw blood samples, and Pixel by LabCorp, which allows consumers to order blood tests online with samples drawn at a nearby lab, and then access their results online. These companies and others allow consumers to learn about their health—from cholesterol levels to Lyme disease antibodies—while bypassing the traditional involvement of a health care professional. Once technical barriers to widespread adoption of p-Tau blood testing are overcome, DTC p-Tau blood testing cannot be far off. Of course, this will not be without controversy. But DTC testing companies have moved to meet consumer demand in the face of controversy before.

DTC testing reveals the importance individuals place on self-determination. It also exposes disagreements about the propriety of taking testing out of health care professionals’ hands and placing it in consumers’. For instance, when the first home pregnancy test came to the market, shortly after Roe v. Wade, proponents heralded it as “a private little revolution,” whereas opponents worried women couldn’t be trusted to take the test alone.² Millions of American women have subsequently used home pregnancy tests to take charge of their well-being and speed the delivery of life-altering information that allows them to make myriad decisions such as whether to pursue prenatal care or obtain an abortion. Home HIV testing charted a similar course, illustrating again how self-determination enhancing breakthroughs often meet resistance before acceptance.

Consumers worried about their risk of having AD and developing dementia will doubtlessly be drawn to DTC p-Tau blood tests that promise diagnostic, even prognostic, information. In a 2016 survey of older adults, seventy-five percent stated they would take a “definitive test predictive” of AD.³ In this respect, DTC p-Tau blood tests could prove more appealing to consumers and more controversial amongst health care professionals than DTC APOE tests. 23andMe’s Personal Genome Service Test, which reports on APOE e4 variants associated with late-onset AD, has met with provider skepticism because clinical guidelines recommend against APOE testing to predict lifetime risk of AD dementia due to the fact that carrying APOE e4 alleles is neither necessary nor sufficient for AD dementia, that it is difficult to convey probabilistic risk, and that we lack preventive options.⁴

Even if the information is imprecise and even in the absence of a disease-modifying therapy for AD, the insights afforded by DTC p-Tau blood tests will be valued by consumers—and therefore be valuable to companies—because dementia uniquely affects identity, autonomy, and capacity. Information allows a person to plan, to have a say in the future before the ability to have a say is lost. Studies suggest that receiving a positive amyloid PET scan result prompts individuals to revise and reimagine their plans.⁵ They retire sooner and travel more, downsize or move in with adult children, and engage in financial as well as estate planning. The result also informs end-of-life planning: expressing wishes to family, drafting advance directives, and less frequently, contemplating suicide. Receiving positive p-Tau blood test results could reasonably be expected to have similar effects. Notably, concerns that suicide might follow in the wake of unwanted results arose in the early days of home pregnancy and HIV testing, though they were ultimately unfounded.

Knowledge is of course power, but power is exercised within a system. Self-determination unfolds in the context of an individual’s choices and options. Consumers’ likely enthusiasm for a DTC p-Tau test ought, therefore, to be tempered by recognition of the ethical and social challenges facing aging Americans and their families. Three challenges that will be exacerbated by DTC p-Tau testing demand our attention: health care system burden, deficient non-discrimination protections, and AD stigma.

First, a DTC p-Tau blood test could advance state and federal goals to improve AD screening and increase diagnostic rates, just as self-testing for HIV has improved testing rates and led to earlier diagnosis. Yet, a DTC p-Tau test cannot address other shortcomings in the health care system and may, in fact, further tax it. Consumers will absorb nominal out-of-pocket costs associated with DTC p-Tau blood testing. The health care system, though, will incur significant costs and burdens associated with follow-up of positive results. For instance, as FDA considers approving aducanumab, we should anticipate high demand for expensive off-label prescribing amongst cognitively unimpaired older adults with positive p-Tau blood test results. Such consumer-driven demand foregrounds the urgent need to build a system that provides excellent, evidence-based memory care.

Second, DTC p-Tau testing will amplify concerns about privacy and discrimination. Medical testing companies are not necessarily subject to the Health Insurance Portability and Accountability Act. Confidentiality is a concern, as consumers may not realize that their data are a valuable commodity—for example, a DTC testing company may seek to sell it to third parties. Individuals might reasonably use a DTC p-Tau blood test result to plan for long-term care services and supports, reducing personal and societal burdens stemming from our nation’s long-term care crisis. However, given that current laws offer limited protections against biomarker-based discrimination, insurers could use the same p-Tau blood test results that inform consumers to refuse them life, disability, or long-term care insurance.⁶ Employers may also discriminate, as it is unclear the Americans with Disabilities Act covers those with elevated biomarkers. Clearly, a DTC p-Tau blood test needs to be coupled with policies to protect those with AD pathology.

Finally, there is a substantial stigma of AD. For individuals worried about stigmatization if they undergo p-Tau testing in traditional venues, the privacy afforded by DTC testing may hold particular appeal, similar to the appeal of home HIV testing. However, DTC p-Tau blood testing may also cause AD stigma to spill over to those with positive results, whether by changing self-perceptions or how others perceive them. A recent survey experiment showed that, even in the absence of cognitive symptoms, a positive AD biomarker result evokes stronger stigmatizing reactions than a negative result.⁷ Stigma is a harm that must be mitigated through public health messaging and compelling counter-narratives.

The value of a DTC p-Tau blood test will be the ability to deliver powerful knowledge in service to self-determination. This power is, however, unleashed in a society unprepared to care and liable to discriminate and stigmatize. What kind of society is this that enriches consumers’ understanding—and lines DTC testing companies’ pockets—but impoverishes our collective well-being? DTC p-Tau blood testing seems inevitable, making it more urgent than ever to address the attendant social and ethical challenges and to advocate for policy change.