Sensitivity vs. specificity: A practical guide for using Alzheimer’s disease blood tests

Blood tests for Alzheimer's disease are making headlines—and for good reason. Diagnosis of this disease was once a lengthy and complex process but now involves lab systems that can accurately quantify tiny biological signals in the blood that are associated with Alzheimer's disease pathology. Today, these signals can provide valuable insights for patients and providers by guiding and expediting care in ways that were unimaginable a decade ago. 

One of the most clinically meaningful applications of this progress is the ability to detect amyloid and tau pathology through blood testing. Since 2023, Labcorp has launched several amyloid- and tau-specific lab tests. Identifying and quantifying these proteins in symptomatic patients is important because their accumulation is considered a hallmark of Alzheimer’s disease. While there’s still much to learn, researchers and clinicians now believe the accumulation of these proteins results in inflammation in the brain, leading to the symptoms commonly associated with Alzheimer’s disease. This growing understanding of Alzheimer’s biology has paved the way for new diagnostic tools, including both FDA-cleared and laboratory-developed blood tests (LDTs) (explore the definitions, nuances and common misperceptions of FDA-cleared lab tests and LDTs in our recent article). 

In light of these new blood tests, many industry and advocacy organizations have published related clinical practice guidelines and minimum performance test requirements. Understanding how to use these powerful tools is imperative to providing the best patient care possible. Furthermore, establishing performance standards for Alzheimer’s blood tests provides a benchmark for their sensitivity and specificity along with their positive predictive values and negative predictive values (PPVs, NPVs). But what are sensitivity and specificity and how are they different from PPV and NPV? Here’s what to know. 

What are sensitivity and specificity?

Clinical sensitivity refers to a test’s ability to correctly identify individuals who have a disease (true positives), while minimizing the number of missed cases (false negatives). Clinical specificity refers to a test’s ability to correctly identify individuals who do not have the disease (true negatives), while minimizing incorrect positive results (false positives). Sensitivity and specificity are expressed as a percentage and reflect the test’s performance. 

When a lab test is being developed and validated, the measure of sensitivity and specificity depends on the clinical characteristics of the patients studied and where the performing lab establishes the reference interval or cutoff of what is considered normal vs. abnormal, or positive vs. negative. For Alzheimer’s blood tests, performance is typically evaluated  against results of amyloid PET imaging, which serves as the reference standard for diagnosis and clinical trial endpoints. The placement of this cutoff directly influences the test’s sensitivity and specificity. 

To make this clearer, think of sensitivity and specificity in terms of a home security system that you activate while you’re away or on vacation. Sensitivity is the likelihood of the alarm going off when someone tries to break in (this is a true positive) versus the percentage likelihood that someone breaks in without triggering the alarm (a false negative). 
Specificity, on the other hand, is the percentage likelihood that the security system remains off while the home is secure (a true negative) versus the likelihood the alarm inadvertently goes off because a cat walks by the window or a gust of wind shakes a door (a false positive). 

So, there’s a give-and-take. Where a reference interval or cutoff point for a disease-free subject is set will determine the sensitivity and specificity of the test. For Alzheimer’s blood tests, this decision influences not only test performance but also when and how the test should be used in clinical practice. 

Recommendations for sensitivity and specificity of Alzheimer’s blood tests

The performance thresholds of Alzheimer’s blood tests, as published by the Global CEO Initiative on Alzheimer’s Disease (CEOi) and the Alzheimer’s Association, recommend that, for confirmation of Alzheimer’s disease in a secondary care setting, an Alzheimer’s test should meet or exceed a 90% sensitivity and 90% specificity. 

• >90% sensitivity means that an Alzheimer’s blood test should correctly categorize >90% positive cases as being positive (true positive compared to PET). Subsequently, it also means there should be <10% of positive cases not detected and incorrectly categorized as negative (false negatives compared to PET)
• >90% specificity means that an Alzheimer’s blood test should correctly categorize >90% negative case as being negative (true negative compared to PET). Subsequently, it also means there should be <10% of negative cases being incorrectly categorized as positive (false positives compared to PET)

If you’re thinking that a test’s sensitivity sounds a lot like the positive predictive value (PPV) and that specificity sounds a lot like the negative predictive value (NPV), you’d be right—well, almost. 

What are PPV and NPV? 

Sensitivity/specificity and PPV/NPV are closely related, but the difference is that PPV and NPV calculations may also consider the prevalence of disease. This would include the prevalence of disease in specific care settings, i.e. primary care clinic versus a neurology clinic.

According to the Alzheimer’s Association, 7.2 million Americans age 65 and older are living with Alzheimer's in 2025 — about 1 in 9, or roughly 11% of the population. But prevalence isn’t static; it changes depending on the clinical context. For example, in neurology clinics where patients may be referred to understand their cognitive symptoms, the prevalence of Alzheimer’s is much higher than in the general population. In contrast, primary care settings typically see a lower prevalence, even among symptomatic patients. 

This distinction in care settings and the related prevalence of disease is critical in Alzheimer’s blood tests because it directly affects the pre-test probability of disease and therefore PPV and NPV. Because of this, a test with fixed sensitivity and specificity will yield different predictive values depending on the population it’s used in. We’ll tackle the topic of “pre-test probability” in an upcoming article. 

Real-world example: Lumipulse® pTau-217/Beta Amyloid 42 Ratio

In May 2025, the Lumipulse® pTau-217/Beta Amyloid 42 Ratio test was granted clearance by the FDA with the intended use of aiding certain healthcare providers identify patients with amyloid pathology associated with Alzheimer’s disease. The test has a PPV of 91.8% and NPV of 97.3% and is indicated for adult patients aged 50 years and older, presenting at a specialized care setting with signs and symptoms of cognitive decline. 

Two key elements in the test’s indication are worth highlighting: 1) “specialized care setting” and 2) “symptoms of cognitive decline.” These criteria matter because using the test outside of this context—such as in asymptomatic patients, in primary care, or both—can reduce its predictive value, changing the likelihood of false positives or false negatives.

Lumipulse pTau-217/Beta Amyloid 42 Ratio and its reference interval was studied and validated in a group of individuals with known Alzheimer’s status and disease prevalence intended to mimic a neurological care setting. As a result, applying the test in a lower-prevalence setting, like primary care, would statistically lower PPV and increase NPV, which is why theLumipulse test is not indicated for use in primary care. 

Similarly, using the test to broadly screen asymptomatic individuals would not yield reliable results. The test was not studied in that population, so predictive values would not apply.

How do these tests impact the future of primary care evaluations for Alzheimer’s disease?

In October 2025, Roche’s Elecsys pTau-181 became the second FDA-cleared blood test for Alzheimer’s and the first with a primary care indication. The test was cleared as a rule-out test for Alzheimer’s disease in primary care. This means that within individuals with known cognitive impairment, the Elecsys pTau-181 could rule out, or exclude, the presence of the pathology associated with Alzheimer’s. This was achieved by studying and validating the test within a cohort of individuals that more closely resembled the disease prevalence in primary care (less prevalence of disease) and setting the test’s reference interval to better identify individuals less likely to have disease (greater specificity and greater NPV). So while the PPV of the Elecsys pTau-181 is only 22.4%, the NPV is 97.9%. 

The Elecsys pTau-181 is expected to be available from Labcorp in early 2026. Later in the year, we also anticipate the first clinical practice guidelines that will provide guidance for how Alzheimer’s blood tests should be used in primary care.  
Undoubtedly, the field of Alzheimer’s care will continue to evolve and change as new therapeutic options are studied and new biomarker targets are identified and validated. At Labcorp, we remain committed to being at the forefront of the field, delivering innovative tools for Alzheimer’s disease and other neurodegenerative conditions.

Explore more of our featured tests for neurodegenerative diseases or schedule a meeting to discover how Labcorp can meet your neurology needs.