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A combined blood test for cognitive decline has a 90% accuracy rate in determining whether memory loss is due to Alzheimer’s disease, a new study found.
In comparison, neurologists and other memory specialists correctly diagnosed Alzheimer’s in 73% of their cases. Primary care doctors had even less success, with only a 61% accuracy rate, according to the study.
One part of the blood test — called plasma phosphorylated tau 217, or p-tau217 for short — is one of several blood biomarkers scientists are evaluating for use in the diagnosis of mild cognitive impairment and early-stage Alzheimer’s disease.
The test measures tau protein 217, which is an excellent indicator of amyloid pathology, said study coauthor Dr. Sebastian Palmqvist, an associate professor and senior consultant neurologist at Lund University in Sweden.
“Increases in p tau-217 concentrations in the blood are quite profound in Alzheimer’s disease. At the dementia stage of the disease, levels are more than 8 times higher compared with elderly without Alzheimer’s,” Palmqvist wrote in an email.
Research published in January found a similar p-tau217 test is up to 96% accurate in identifying elevated levels of beta-amyloid and up to 97% accurate in identifying tau. The presence of beta-amyloid and tau tangles in the brain are hallmark signs 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 the amyloid and tau tests, called the amyloid probability score, was the most predictive.
“We’d love to have a blood test that can be used in a primary care physician’s office, functioning like a cholesterol test but for Alzheimer’s,” said Dr. Maria Carrillo, chief science officer of the Alzheimer’s Association.
“The p-tau217 blood test is turning out to be the most specific for Alzheimer’s and the one with the most validity. It seems to be the front-runner,” said Carrillo, who oversees the association’s research initiatives, which included partial funding for the new study.
Once fully vetted, highly accurate blood tests could “change the game in the speed in which we can conduct Alzheimer’s trials and get to the next new medication,” she said. “These are absolutely transformational times.”
How does a p-tau217 blood test work?
The peptide p-tau217 is unique in that it can be detected only when amyloid plaques are present in the brain, Carrillo said.
“What that means to us scientifically is that when we’re measuring p-tau217, we’re measuring the neuronal damage from tau very early on in Alzheimer’s, but only when amyloid is already present,” she said.
“You’re not really measuring amyloid, but the test is telling you it’s there, and that’s been backed up with objective PET (positron emission tomography) scans that can see amyloid in the brain,” Carrillo said. “It’s a beautiful marker for Alzheimer’s: If you don’t have amyloid present, you don’t have Alzheimer’s. If you have elevated tau in your 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 FTD, or frontal lobe dementia. In FTD, tau tangles attack the brain’s frontal lobe, 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 controlling memory, but amyloid plaques play a key role. Small clusters of plaques can gather at synapses and interfere with the nerve cells’ ability to communicate. Amyloid plaques may also overstimulate the immune system, triggering inflammation that may further damage the brain.
Some of the newest drugs for dementia, such as lecanemab and donanemab, target beta-amyloid and are thought to be less effective in people with advanced tau pathology, experts say.
Because deposits of amyloid can begin accumulating in the brain decades before symptoms begin, even when a person is in their 30s or 40s, an early diagnosis of brain amyloid could be critical for lifestyle modifications and preventive treatment with medications.
Current screening tests are inconclusive
The study, published Sunday in the journal JAMA Neurology, followed 1,213 people with an average age of 74 who were undergoing cognitive evaluations in both primary care and specialty clinics in Sweden.
Each person’s blood was tested using p-tau217, and the results were combined with blood measures of beta-amyloid 40/42 to develop a final score.
“When you use a combination of the 40 to 42 ratio and p-tau217, it increases the diagnostic accuracy of p-tau217,” said preventive neurologist Dr. Richard Isaacson, director of research at the Institute for Neurodegenerative Diseases in Florida, who was not involved in the study.
The 90% accuracy of the study’s combined blood test was confirmed via a spinal fluid tap, which along with an amyloid PET scan is currently the only gold-standard scientific method other than autopsy for diagnosing Alzheimer’s. Both tests are expensive, invasive and not readily available across the United States, experts say.
The results of the blood tests were then measured against patient diagnoses provided by Swedish primary care doctors and specialists. The relatively poor rate of accuracy — 61% and 73% — highlights how difficult it is for doctors to correctly identify Alzheimer’s pathology with current tools: a short interview with the patient, a brief cognitive test and a computed tomography, or CT, scan of the brain.
“Generally, both traditional paper-and-pen tests and digital cognitive assessments are not highly accurate in specifically identifying Alzheimer’s disease,” said study coauthor Dr. Oskar Hansson, a professor and senior consultant of neurology at Lund University.
“Many other conditions and diseases can present similar cognitive symptoms, leading to potential misdiagnosis or missed diagnosis,” 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 disease, Hansson said. Diseases that may affect cognitive function include vascular dementia, depression, thyroid disease, sleep apnea and even vitamin B12 deficiency.
If those mimics are not caught during the initial exam, people with no Alzheimer’s pathology can clog up waiting lists for specialists and appointments for spinal taps and amyloid PET scans, Carrillo said.
By the time someone with true amyloid pathology sees a specialist, she added, they may “fall out of that window of being eligible for the drugs 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 US population. By 2033, if a primary care doctor uses only the current cognitive assessments to determine dementia, people will wait an average of nearly six years before finding out whether 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 are used, wait times may drop 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 routinely pop up in your primary doctor’s office anytime soon, however. More research is needed to verify the positive results appearing in studies, guidelines for physician use must be established and distributed, and physicians have to be educated about any possible nuances, Isaacson said.
“There’s no one more bullish on these tests than I am, but Alzheimer’s blood tests aren’t fully definitive yet,” he said. “If it is 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 borderline, we still don’t know what that means.”
In the meantime, research has shown there are many actions people can take to prevent or slow cognitive decline, including getting regular exercise, eating a Mediterranean-style diet and treating vascular risk factors like high blood pressure, high cholesterol and diabetes.
“It’s our goal to use only the highest-quality blood tests to not only help make an early diagnosis of Alzheimer’s but also evaluate response to risk-reducing interventions,” Isaacson said. “These are very hopeful times.”
Correction: Clarification: This story has been updated to clarify the Alzheimer’s Association’s role in the new study.