Alzheimer’s Blood Tests – What You Need to Know in 2023
Scientifically reviewed by: Sharyn Rossi, PhD, BrightFocus Foundation
Worldwide, at least 50 million people are believed to be living with Alzheimer's disease or other dementias, and accuracy and timing of diagnosis are critical. In the United States, Alzheimer’s blood tests are now available as another tool that can provide highly accurate, direct evidence of amyloid buildup in the brain earlier and faster than before. This makes it possible for people with Alzheimer’s to move on to next steps, such as learning about the disease, finding the right care team, making healthy lifestyle changes to protect their brain, and starting beneficial treatments.
To diagnose Alzheimer’s disease, qualified providers and specialists should conduct a thorough assessment of the individual and perform standard neuropsychological assessments as part of their evaluation toolbox. These cognitive examination aids, along with other screening methods such as cerebrospinal fluid (CSF) analysis or brain imaging using positron emission tomography (PET) scans, can check for Alzheimer’s biomarkers and toxic protein buildup in the brain.
In a primary care setting, however, it is often difficult for providers who do not have expertise in neurological disorders to discuss diagnostic or treatment options with their patients. Blood tests can help to rule out Alzheimer’s as a cause of an individual’s memory decline, prompting the clinician to search for other conditions that may be treatable or even reversible.
The Alzheimer’s Disease Research program at BrightFocus Foundation provided grant support for the first Alzheimer’s blood test to come to market: the PrecivityAD test, which became commercially available in the U.S. in late 2020. The test can be ordered by physicians in 49 states, Puerto Rico, and the District of Columbia (certification is pending in New York) at a cost of $1,200. The test is not covered by private or public insurers (e.g., Medicare and Medicaid), but its developer, C2N Diagnostics, offers financial assistance options.
How the tests work
PrecivityAD works by measuring the ratio of two types of amyloid-beta (Aß) protein in the blood: Aß40, the most prevalent type in the brain, and Aß42, which is less prevalent in the brain but makes up the majority of Aß protein found in Aß plaques. The test also measures apolipoprotein E (ApoE) variants in the blood to determine whether a person carries the APOE4 mutation, which raises the risk for brain Aß accumulation and Alzheimer’s disease.
The Aß42/40 ratio, combined with a person’s age and APOE genotype, determines an amyloid probability score. The score is sorted into ranges indicating a low, intermediate, or high likelihood of Aß plaques consistent with an Alzheimer’s diagnosis.
Another test that measures Aβ42/40 ratio in the blood is Quest Diagnostics’ AD-Detect Amyloid Beta 42/40 Ratio test. Introduced in May 2022, the test costs $500, is covered by certain health insurance plans, and can be ordered by physicians.
These blood tests—and many others still in development—use special lab equipment to directly measure trace amounts of Aβ in blood samples. C2N, for example, processes the tests onsite at its own federally regulated (CLIA certified) lab.
The field is growing, and researchers are still discovering new blood-based biomarkers to detect Alzheimer’s and techniques to pinpoint the biomarkers. For example, a team of Japanese researchers recently announced early results using a biosensing technology to detect Aβ-binding exosomes (i.e., small particles released by cells) in blood that increase as Aβ accumulates. So far, their research has been limited to Alzheimer’s mice models, but they hope to develop the technology further.
Enter p-tau, a new blood biomarker
Several new blood tests in development measure tau, another brain protein involved in Alzheimer’s disease. These tests measure tau that has undergone molecular changes, known as phosphorylation, which correlates with Alzheimer’s disease. A recent study showed that one form of phosphorylated tau (p-tau) blood tests can detect the earliest stages of Alzheimer’s, even before Aß was detected via PET scan.
Experts have long debated whether Aß or tau is more indicative of Alzheimer’s, but now the two camps have merged, said BrightFocus Alzheimer’s Disease Research grantee Thomas K. Karikari, PhD, a researcher at the University of Pittsburgh and the University of Gothenburg, Sweden, who was involved in the discovery and development of tau-based Alzheimer’s biomarkers from their earliest stages.
“Tau is much more intriguing than we initially thought,” he said. “There are some forms that we think get released earlier, when amyloid starts to kick in, and there are other forms that kick in later.”
In fact, the field has quickly progressed to the point where tau biomarkers can be targeted to almost any stage of Alzheimer’s, from the earliest Aß accumulation to advanced neurodegeneration, which can span 20 years or longer.
Currently, only one Alzheimer’s blood test using a p-tau biomarker is commercially available: the Simoa p-Tau181 test developed by Quanterix Corporation and launched in July 2022. Like the other tests, it can be ordered by physicians but is not yet reimbursable from public and private health plans. Dr. Karikari was involved in its development and, more recently, in a test using p231, which some experts said has the potential to become the earliest specific plasma marker of Alzheimer’s disease pathology.
Another test—PrecivityAD2, the latest iteration of the existing PrecivityAD blood test—measures tau in addition to the ratio of two types of amyloid-beta in the blood. The new test is expected to launch in 2023.
Accuracy of tests vary according to populations studied
Despite recent progress, there are a few hurdles to overcome before Alzheimer’s blood tests are ready for widespread use. Data on their accuracy comes almost exclusively from clinical trials, where participants tend to be alike in age, race, and ethnicity, as well as Alzheimer’s risk factors. In community settings, people taking the test would vary in all these aspects.
A recent study evaluated the use of P-tau181 and P-tau217 blood biomarkers among patients enrolled in the Mayo Clinic Study of Aging. It showed that results were not as accurate as those previously reported in patients seen in specialized memory clinics, and that multiple comorbidities, including chronic kidney disease or a history of myocardial infarction or clinical stroke, were associated with higher plasma p-tau levels, which in some cases produced a false positive result.
Experts have said larger studies are needed, especially in diverse populations, before taking the tests into the clinic. Dr. Karikari and Suzanne Schindler, MD, a neurologist at Washington University School of Medicine in St. Louis, voiced these concerns in a commentary about the Mayo study findings.
These issues and others continue to fuel a debate that led an Alzheimer’s Association Global Working Group to recommend against the use of Alzheimer’s blood tests in primary care settings at this time. Instead, it called the blood tests an important tool for clinical research and backed their “cautious initial use” in specialized memory clinics. The recommendations were published in Alzheimer’s & Dementia in July 2022.
Taking Alzheimer’s blood testing into primary care
Other experts have called for several practical steps to pave the way for Alzheimer’s blood tests to be used in primary care. They include Doug Galasko, MD, a neurologist and Alzheimer’s clinician at the University of California, San Diego, and a longtime member of the BrightFocus ADR Scientific Review Committee.
Dr. Galasko said several medical resources need to be in place for patients to truly benefit from Alzheimer’s blood tests. First, blood tests must be used in conjunction with cognitive testing, which he calls a “vital sign” of brain health.
“Many primary care doctors lack the time or expertise to test cognition consistently,” Dr. Galasko said.
He also warned that an Alzheimer’s blood test “is not some simple, check-off-a-box blood test.” Physicians might need to discuss the test, its context, and possible outcomes with a patient before ordering it. He added that once the results are in, an in-depth conversation about interpretation, prognosis, and potential treatment options will need to occur.
C2N, for instance, offers training with its PrecivityAD blood test that covers assessment before ordering the test and one-on-one consultation with company experts, if needed, as physicians interpret and share results with patients.
Physicians who think their patients would benefit from an Alzheimer’s blood test will be able to provide better care if they are prepared in advance, Dr. Galasko said. However, “as of now, such analysis and discussion are beyond the scope of most busy primary care doctors, and even some dementia specialists,” he said.
The bottom line
Although Alzheimer’s blood tests are becoming more available in the U.S., physicians and experts are raising a flag of caution around their use. Patients interested in the tests should discuss it with their doctor. If the doctor is not comfortable ordering the test, they might be able to refer the patient to a memory clinic or Alzheimer’s Disease Research Center where the tests are used. Another option is joining a clinical trial or study where Alzheimer’s blood tests are used to screen participants.
About BrightFocus Foundation
BrightFocus Foundation is a premier nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma. Through its flagship research programs—Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research—the Foundation is currently supporting a $75 million portfolio of 287 scientific projects. BrightFocus has awarded nearly $275 million in groundbreaking medical research funding since inception and shares the latest research findings, expert information, and English/Spanish disease resources to empower the millions impacted by these devastating diseases. Join our community at brightfocus.org.
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