Laboratory companies seeking to offer Alzheimer’s blood tests must prove three core things: that their test accurately measures what it claims to measure (analytical validity), that the measurement correlates with actual brain disease or cognitive decline (clinical validity), and that the test results actually help guide patient care or predict future decline (clinical utility). These aren’t academic boxes to check—they determine whether a test can be marketed, recommended by neurologists, or covered by insurance. A lab might develop a highly sensitive assay for blood phosphorylated tau, for example, but still need years of patient data showing that the result predicts cognitive decline and influences treatment decisions before it becomes clinically useful.
The U.S. Food and Drug Administration (FDA) has become increasingly stringent about what counts as proof, especially as the number of Alzheimer’s blood test companies has grown. Between 2022 and 2025, several companies—including C2N Diagnostics (with PrecivityAD), Eli Lilly (with Preclinical AD Index), and Roche—have submitted or received FDA clearance for Alzheimer’s biomarker tests, each requiring thousands of participant samples and years of validation studies. The rules are similar for labs using CLIA certification (Clinical Laboratory Improvement Amendments) without FDA oversight, though CLIA labs face less regulatory pressure and sometimes market tests with thinner evidence than FDA-approved counterparts.
Table of Contents
- What Does “Analytical Validity” Mean for Alzheimer’s Blood Tests?
- Clinical Validity—Does the Biomarker Actually Reflect Brain Pathology?
- Clinical Utility—Will the Test Result Change How a Patient Is Treated?
- What Regulatory Pathways Do Lab Companies Use?
- Race, Ethnicity, and Biomarker Bias—A Growing Concern
- How Do Labs Gather the Evidence?
- What Should Patients Know When Considering an Alzheimer’s Blood Test?
- Frequently Asked Questions
What Does “Analytical Validity” Mean for Alzheimer’s Blood Tests?
Analytical validity means the test reliably and repeatedly measures the specific biomarker it claims to measure—usually amyloid-beta, phosphorylated tau, or total tau in blood plasma or serum. To prove this, labs must show that their assay produces the same result when the same sample is tested multiple times (reproducibility), that it works accurately across a range of concentrations (linearity), and that it doesn’t give false readings due to interference from other proteins or substances in the blood. For instance, a company developing a plasma phosphorylated tau-181 test must demonstrate that their immunoassay reliably detects tau-181 phosphorylation in the same sample whether it’s tested on day one or day fifteen, and whether the sample is run by technician A or technician B.
The technical bar here is high but achievable, and most serious lab companies clear it because analytical validity is purely a matter of instrument performance and quality control. Where problems arise is when labs skip publishing these data or submit fda applications with insufficient analytical validation data. Some CLIA labs have launched tests with minimal or proprietary analytical validation, making it impossible for physicians or patients to assess whether the test is trustworthy. Roche’s cobas plasma phosphorylated-tau217 test, cleared by FDA in 2023, included detailed analytical validation across multiple patient populations; by contrast, a handful of smaller labs have marketed similar tests with limited public documentation of analytical performance.
Clinical Validity—Does the Biomarker Actually Reflect Brain Pathology?
Clinical validity requires showing that the biomarker measured in blood correlates with the actual pathological changes in the brain (amyloid plaques and tau tangles seen on autopsy or PET imaging) or with cognitive decline over time. This is harder to prove than analytical validity because it requires long-term follow-up studies of hundreds or thousands of participants, many of whom must eventually undergo PET brain imaging, cognitive testing, or autopsy. A company might prove that their test detects plasma phosphorylated tau accurately (analytical validity), but if that measurement doesn’t correlate with tau PET burden in the brain or doesn’t predict future cognitive decline, it has no clinical validity. Several studies published between 2020 and 2024 have established clinical validity for some Alzheimer’s blood biomarkers.
For example, research in the journal Neurology showed that plasma phosphorylated tau-181 levels correlate with tau pathology on brain PET imaging and predict cognitive decline in cognitively normal older adults. However, clinical validity isn’t uniform across all populations. Studies have found that some biomarkers perform differently in people of African descent, Asian descent, or other racial and ethnic groups, raising the concern that a test validated primarily in white populations may be less reliable for other groups. This limitation—racial and ethnic bias in biomarker research—has led some organizations, including the National Institute on Aging, to call for more diverse validation cohorts.
Clinical Utility—Will the Test Result Change How a Patient Is Treated?
Clinical utility is the hardest requirement to prove, and it’s where many promising biomarkers fall short. A test has clinical utility only if the result meaningfully influences diagnosis, prognosis, treatment decisions, or patient management. For example, a positive amyloid-beta and tau test in a cognitively normal person might prompt earlier screening for cognitive decline, counseling about lifestyle interventions, or enrollment in clinical trials for anti-amyloid drugs—actions that wouldn’t happen without the test result. Conversely, a test that simply confirms what neurologists already know from cognitive testing and MRI may have limited clinical utility, because the result doesn’t change care.
The FDA’s 2023 clearance of PrecivityAD (C2N Diagnostics) required evidence that the test result influenced physician behavior and patient decisions about screening and early intervention. Similarly, Eli Lilly’s Preclinical AD Index was validated in studies showing that the test could identify cognitively normal individuals at high risk of future decline. But this is an evolving bar. A test cleared by FDA five years ago might not meet today’s clinical utility standards, and many CLIA labs market tests without publishing evidence that the results actually change outcomes. Insurance companies, including Medicare, have started requiring explicit clinical utility data before covering tests—a shift that pushes labs to prove their tests are worth the cost.
What Regulatory Pathways Do Lab Companies Use?
Lab companies can obtain FDA clearance via the 510(k) pathway (showing their test is substantially equivalent to an already-approved test) or the more rigorous Premarket Approval (PMA) pathway, which requires comprehensive clinical trial data. Alternatively, labs can operate under CLIA certification without FDA approval, provided they don’t make claims about clinical validity or utility. The choice affects how much proof a company must publicly provide. FDA-cleared tests require published or submitted validation data; CLIA-only labs can keep their validation studies proprietary and unpublished.
C2N Diagnostics pursued FDA clearance for PrecivityAD, investing millions in large multi-site studies and submitting thousands of pages of data. The company spent years validating the test in both cognitively normal individuals and those with mild cognitive impairment, ultimately securing FDA clearance in 2023. By contrast, some regional or smaller labs offer Alzheimer’s biomarker tests under CLIA certification alone, claiming analytical validity internally but not submitting to FDA oversight. This creates a two-tier market: FDA-cleared tests with published validation data, and CLIA-only tests where physicians and patients have limited visibility into the proof. Neither pathway is inherently wrong—FDA clearance provides accountability; CLIA alone allows innovation with less regulatory burden—but the trade-off is that patients and doctors must do more due diligence to assess CLIA-only tests.
Race, Ethnicity, and Biomarker Bias—A Growing Concern
As Alzheimer’s blood tests have proliferated, it’s become clear that many biomarkers were validated in predominantly white cohorts, raising questions about whether cutoff values and predictive accuracy apply equally to other populations. A plasma phosphorylated tau threshold that predicts cognitive decline in white older adults might not be the same cutoff for Black older adults or Hispanic older adults, yet many labs use a single universal cutoff. This isn’t merely an academic problem—it means a test could underdiagnose disease in some populations and overdiagnose in others, leading to disparities in who gets screened, counseled, and treated.
The Alzheimer’s Association and the National Institute on Aging have both flagged this problem in recent guidance documents, recommending that companies validate tests across diverse populations before marketing them widely. Some newer validation studies, particularly those conducted at major research centers with diverse participant populations, have begun addressing this gap. However, many existing tests were cleared based on validation data from predominantly white cohorts, and companies face no regulatory requirement to go back and re-validate in other populations. This means a physician using a biomarker test should be aware that the evidence supporting that test may not apply equally to all their patients.
How Do Labs Gather the Evidence?
Most companies gather clinical validity and utility data through observational cohort studies, where they recruit hundreds of older adults (both cognitively normal and those with mild cognitive impairment or dementia), collect blood samples, conduct cognitive testing, and follow participants over years to see who develops decline or dementia. Some labs also partner with existing research cohorts like the Framingham Heart Study or the Alzheimer’s Disease Neuroimaging Initiative (ADNI), accessing decades of follow-up data. A few labs have invested in prospective randomized trials, randomizing people to receive biomarker testing versus usual care and measuring whether biomarker-guided interventions improve outcomes—a gold standard but one that takes a decade or longer to complete.
The cost of this evidence is substantial. Large validation studies can cost millions of dollars, involve thousands of participants, and take five to ten years to completion. For a smaller lab or startup, this barrier is real, which is why many companies either partner with academic medical centers (which contribute the participants and longitudinal follow-up) or operate under CLIA without FDA oversight, reducing the evidentiary burden.
What Should Patients Know When Considering an Alzheimer’s Blood Test?
When a doctor offers an Alzheimer’s blood test, patients should ask whether the test is FDA-cleared or CLIA-only, whether it’s been validated in a published, peer-reviewed study, and whether the result will actually affect their care. An FDA-cleared test like PrecivityAD or the Roche phosphorylated tau-217 assay has passed regulatory scrutiny and has published validation data that physicians can review. A CLIA-only test may be reliable, but the lab isn’t required to publish its validation data, so the evidence is harder to evaluate.
Patients should also understand that a positive result for amyloid and tau doesn’t mean someone has Alzheimer’s disease—it means they have pathology that may lead to cognitive decline in the future, and the timeline varies widely from years to decades. Some people with significant amyloid and tau pathology never develop noticeable cognitive symptoms. Additionally, patients should be aware that insurance coverage for Alzheimer’s blood tests is still evolving. Medicare and some commercial insurers now cover certain FDA-cleared tests like PrecivityAD and plasma phosphorylated tau tests when ordered by a neurologist or dementia specialist for cognitive evaluation, but CLIA-only tests may not be covered, leaving patients responsible for out-of-pocket costs, which can range from $500 to $3,000 per test.
Frequently Asked Questions
What’s the difference between analytical validity and clinical validity?
Analytical validity means the test accurately measures the biomarker (e.g., reliably detects tau in blood). Clinical validity means the biomarker correlates with actual brain disease or cognitive decline. A test can have strong analytical validity but weak clinical validity if the measured biomarker doesn’t predict disease.
Does a positive Alzheimer’s biomarker test mean I have Alzheimer’s disease?
No. A positive test shows you have amyloid and/or tau pathology in your brain, which may lead to cognitive decline in the future, but many cognitively normal people have significant pathology and never develop dementia symptoms.
Are Alzheimer’s blood tests covered by Medicare?
Medicare covers some FDA-cleared tests like PrecivityAD and plasma phosphorylated tau-217 when ordered by a neurologist or dementia specialist for cognitive evaluation. Coverage varies by insurance plan and test, so check with your insurer.
Why do some Alzheimer’s blood tests have different cutoff values?
Different companies use different assays and validation cohorts, which can produce different cutoff values for the same biomarker. Additionally, some cutoffs were validated in primarily white populations and may not apply equally to other racial or ethnic groups.
Can I get an Alzheimer’s blood test from my primary care doctor?
This depends on your doctor and your insurance. Some primary care doctors order these tests, but they’re most commonly ordered by neurologists or geriatricians, and insurance may not cover a test ordered outside that specialty.
What’s the difference between FDA-cleared and CLIA-certified tests?
FDA-cleared tests have undergone federal regulatory review and require published validation data. CLIA-certified tests meet laboratory quality standards but don’t require FDA approval and may not have published validation data. Both can be valid, but FDA-cleared tests have more public accountability.
