Blood test can detect 90% of Alzheimer’s cases, study says

A combined blood test for cognitive decline has a 90 percent accuracy rate in determining whether memory loss is due to Alzheimer’s disease, a new study has revealed.

By comparison, neurologists and other memory specialists correctly diagnosed Alzheimer’s in 73 percent of their cases. Primary care doctors were even less successful, with just 61 percent accuracy, the study found.

One part of the blood test — called plasma phosphorylated tau 217, or p-tau217 — is one of several blood biomarkers that scientists are evaluating for use in diagnosing mild cognitive impairment and early-stage Alzheimer’s.

The test measures the protein tau 217, which is an excellent indicator of amyloid pathology, said study co-author Dr. Sebastian Palmqvist, associate professor and senior consultant neurologist at Lund University in Sweden.

“Increases in blood p-tau217 concentrations are quite profound in Alzheimer’s disease. In the dementia stage of the disease, levels are more than 8-fold higher compared to elderly individuals without Alzheimer’s,” Palmqvist wrote in an email.

Research published in January found that a similar p-tau217 test was up to 96 percent accurate in identifying elevated levels of beta-amyloid and up to 97 percent accurate in identifying tau. The presence of beta-amyloid and tau tangles in the brain are hallmarks of Alzheimer’s disease.

In the new study, the p-tau217 test was combined with another blood biomarker for Alzheimer’s called the amyloid 42/40 ratio, which measures two types of amyloid proteins, another biomarker of Alzheimer’s disease.

The combination of amyloid and tau tests, called the amyloid probability score, was the most predictive.

“We would love to have a blood test that could be used in the primary care physician’s office that would function like a cholesterol test, but for Alzheimer’s,” said Dr. Maria Carrillo, chief scientific officer of the Alzheimer’s Association.

“The p-tau217 blood test is proving to be the most specific for Alzheimer’s and the most valid. It appears to be the leading candidate,” said Carrillo, who oversees the association’s research initiatives, which included partial funding for the new study.

Once fully tested, highly accurate blood tests could “change the game in the speed at which we can conduct Alzheimer’s trials and come up with the next new drug,” she said. “These are absolutely transformative times.”

How does a p-tau217 blood test work?

The p-tau217 peptide is unique in that it can only be detected when amyloid plaques are present in the brain, Carrillo said.

“What this means for us scientifically is that when we are measuring p-tau217, we are measuring neuronal damage caused by tau very early in Alzheimer’s, but only when amyloid is already present,” she said.

“You’re not actually measuring the amyloid, but the scan is telling you it’s there, and that’s been corroborated with objective PET (positron emission tomography) scans that can see amyloid in the brain,” Carrillo said. “It’s a nice marker for Alzheimer’s: If you don’t have amyloid present, you don’t have Alzheimer’s. If you have elevated tau in the brain, however, then we know that’s a sign of another type of dementia.”

Tau tangles are implicated in several other neurological diseases, such as frontotemporal dementia (FTD). In FTD, tau tangles attack the frontal lobe of the brain, causing behavioral and emotional changes and the loss of executive functions, such as planning. Memory loss, if it occurs, happens much later.

In Alzheimer’s, tau tangles build up in the part of the brain that controls memory, but amyloid plaques play a key role. Small clumps of plaque can build up at synapses and interfere with the ability of nerve cells to communicate. Amyloid plaques can also overstimulate the immune system, triggering inflammation that can further damage the brain.

Some of the newer dementia drugs, such as lecanemab and donanemab, target beta-amyloid and are considered less effective in people with advanced tau pathology, experts say.

Because amyloid deposits can begin to build up in the brain decades before symptoms begin, even when a person is in their 30s or 40s, an early diagnosis of brain amyloid can be crucial for lifestyle modifications and preventive drug treatment.

Current screening tests are inconclusive

The study, published on Sunday (28) in the journal JAMA Neurologyfollowed 1,213 people with an average age of 74 who were undergoing cognitive assessments in both primary care and specialist clinics in Sweden.

Each person’s blood was tested using p-tau217, and the results were combined with blood measurements of beta-amyloid 40/42 to develop a final score.

“When you use a combination of the 40/42 ratio and p-tau217, the diagnostic accuracy of p-tau217 increases,” said preventive neurologist Dr. Richard Isaacson, director of research at the Florida Institute for Neurodegenerative Diseases, who was not involved in the study.

The 90 percent accuracy of the study’s combined blood test was confirmed using a spinal tap, which along with an amyloid PET scan is currently the only scientific gold standard method, other than an autopsy, for diagnosing Alzheimer’s. Both tests are expensive, invasive and not widely available in the United States, experts say.

The blood test results were then measured against patient diagnoses provided by primary care physicians and Swedish specialists. The relatively low accuracy rate — 61 percent and 73 percent — highlights how difficult it is for doctors to correctly identify Alzheimer’s pathology with current tools: a brief patient interview, a short cognitive test and a computed tomography, or CT, scan of the brain.

“Generally, both traditional pen-and-paper tests and digital cognitive assessments are not highly accurate in specifically identifying Alzheimer’s disease,” said study co-author Dr. Oskar Hansson, professor and senior consultant in neurology at Lund University.

“Many other conditions and diseases can present with similar cognitive symptoms, leading to potential misdiagnosis or missed diagnoses,” Hansson said in an email.

In fact, between 20% and 30% of patients seen by specialists take medications or have other medical conditions that can mimic Alzheimer’s, Hansson said. Diseases that can affect cognitive function include vascular dementia, depression, thyroid disease, sleep apnea and even vitamin B12 deficiency.

If these mimics aren’t identified during the initial screening, people without Alzheimer’s pathology can clog up waiting lists for specialists and appointments for spinal taps and amyloid PET scans, Carrillo said.

When someone with true amyloid pathology sees a specialist, she added, that person may “fall outside that window of eligibility for the drugs that we have, and that’s terrible.”

When will routine blood tests be available?

Wait times are only going to get worse, according to mathematical models based on the aging of the U.S. population. By 2033, if a primary care physician uses only current cognitive assessments to determine dementia, people will wait an average of nearly six years before finding out if they are eligible for new Alzheimer’s treatments, a new study found. The study was presented Sunday at the 2024 Alzheimer’s Association International Conference in Philadelphia.

However, if accurate blood tests were used, waiting times could fall to between six and 13 months, the study found, because far fewer people would need to see a specialist or undergo additional testing.

Don’t expect blood tests for Alzheimer’s to start routinely appearing in your primary care doctor’s office any time soon, however. More research is needed to verify the positive results that are appearing in studies, guidelines for doctors’ use need to be established and distributed, and doctors need to be educated about possible nuances, Isaacson said.

“There’s no one more optimistic about these tests than I am, but the blood tests for Alzheimer’s are not yet completely definitive,” he said. “If it’s a positive test, it still needs to be confirmed via PET scan or spinal tap. If it’s a negative result, that’s reassuring, but if it’s uncertain, we don’t know what that means yet.”

Meanwhile, research has shown that there are many actions people can take to prevent or slow cognitive decline, including exercising regularly, following a Mediterranean-style diet, and treating vascular risk factors such as high blood pressure, high cholesterol, and diabetes.

“Our goal is to use only the highest quality blood tests to not only help make an early diagnosis of Alzheimer’s, but also assess response to risk-reducing interventions,” Isaacson said. “These are very hopeful times.”

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