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• Posted July 19, 2023

Blood Prick Test for Alzheimer's Shows Promise

A definitive diagnosis of Alzheimer's disease now requires a series of complicated and expensive imaging scans that look for abnormal protein plaques and tangles in the brain.

But in the near future, detecting signs of Alzheimer's could be as simple as taking a finger prick blood test.

Researchers detected key Alzheimer's-related biomarkers in dried blood samples drawn from a finger prick, according to findings presented Wednesday at the Alzheimer's Association International Conference, in Amsterdam.

“The finger prick method is very much a work in progress, but we are encouraged by this preliminary evidence,” said lead scientist Hanna Huber, a postdoctoral researcher of neurochemistry at the University of Gothenburg in Sweden.

This study, along with two other research efforts featured at the conference, point the way to a future when Alzheimer's can be more easily detected, tracked and treated, experts said.

“There is an urgent need for simple, inexpensive, minimally invasive and accessible diagnostic tools for Alzheimer's,” said Percy Griffin, director of scientific engagement for the Alzheimer's Association. “A widely available, simple-to-use blood test for Alzheimer's would be a great advance."

The two other studies involved the usefulness of blood samples to diagnose Alzheimer's, and a new test that could more accurately detect the presence of tau protein tangles in the brain.

“These studies are fascinating and the results inspire hope,” Griffin said. “They point to a not-too-distant future where multiple tools to aid in early detection and accurate diagnosis are more accessible to all people in all communities.”

Alzheimer's disease is defined by two types of proteins that start behaving abnormally in the brain.

Early in Alzheimer's, amyloid beta protein starts to form plaques in the brain. As the disease progresses and cognitive symptoms arise, tau proteins begin twisting into tangles.

Currently, the gold standard way to see if a person's brain contains plaques or tangles is through imaging scans, said Dr. Randall Bateman, a professor of neurology at Washington University School of Medicine in St. Louis and co-senior researcher of the tau test study.

But these plaques and tangles shed protein fragments into cerebrospinal fluid, which can then eventually make their way into a person's bloodstream, Bateman said.

If researchers can figure out a way to efficiently and accurately detect those protein fragments, they can use that data to assess whether someone has Alzheimer's or is at risk for developing the disease in the near future, experts say.

Simple dried blood cards

For the finger prick study, Huber and her colleagues collected blood samples from 77 memory clinic patients at the ACE Alzheimer Center in Barcelona, Spain.

The finger prick samples were transferred onto dry blood spot cards and shipped overnight, without any temperature control, to the University of Gothenburg.

“In the lab in Gothenburg, we extracted the dried blood from the cards and measured proteins that are related to Alzheimer's disease,” Huber said. “These were markers of amyloid and tau pathology, neurodegeneration and glial [brain cell] activity.”

The levels of these markers found in the dried blood samples were about as good as those derived from standard blood analysis using regular blood collection methods, Huber said.

“A blood test from a finger prick requires less sample volume than standard reference methods in plasma,” she said. “Another advantage of the dry blood spot sampling is that there is no need for centrifuges or freezers to store and process the sample.”

Once the test is perfected, doctors in rural areas or at smaller hospitals -- or even average folks -- could take a finger prick blood sample and ship it off to a facility equipped with the highly sophisticated technology needed to detect these markers, Huber said.

“Our next steps will be a validation of our results in a wider memory clinic setting, and we will invite patients and caregivers do the dry blood spot collection themselves,” she said. “This could be in their home or unsupervised in the doctor's office. This will allow us to understand if self-collection is attainable, and if we see the same results compared to the optimal settings as applied in our pilot study.”

In the second study, researchers at Lund University in Sweden investigated the usefulness of blood-based Alzheimer's biomarkers to diagnose the disease in a primary care setting.

The team recruited more than 300 middle-aged to elderly patients at 17 primary care centers in Sweden.

The patients underwent cognitive testing and an imaging scan of their brain, and afterward their personal doctor rendered a diagnosis of their brain health.

A blood sample also was taken and analyzed to estimate each patient's levels of abnormal amyloid beta and tau.

As a last step, the patients underwent a thorough clinical examination at a specialized memory clinic to see how well the primary care doctor and the blood test performed in detecting Alzheimer's.

The blood test correctly diagnosed Alzheimer's or identified the presence of Alzheimer's-related brain changes in more than 85% of cases.

By comparison, primary care physicians got it right about 55% of the time. As a result, more than half of the people who actually had Alzheimer's did not receive treatment, while 30% of people without Alzheimer's received treatment they didn't need.

Tracking a specific type of tau

The third study looked at a better way to detect tau tangles, with researchers at the Washington University School of Medicine in St. Louis and Lund University identifying a form of tau that could serve as a marker to track Alzheimer's progression. Results were published July 13 in the journal Nature Medicine.

The study of more than 660 Alzheimer's patients in the United States and Sweden revealed a specific form of tau in cerebrospinal fluid that tracks accurately with the amount of damaging tau tangles in the brain, as well as a person's degree of mental decline.

“This comes from a part of the tau protein that actually makes up the tangles in the brain,” Bateman said. “The other tau biomarkers come from a part of the protein that doesn't make up the tau tangles, but it gets released in response to the presence of amyloid plaques. In order for us to really track the tangles, we need to get to the part of the protein that actually aggregates in the tangles.”

Using this type of tau, called MTBR-tau243, researchers were able to detect Alzheimer's and accurately assess the stage to which a person's illness had progressed, researchers said.

At this point, the tau test relies on a spinal tap to draw cerebrospinal fluid for analysis, but Bateman thinks it could be translated into a blood test within a few years.

“In the past when we developed these tests for cerebrospinal fluid, it's just taken a few years to move from that to clinical blood tests that can be used in doctor's office,” he said.

But science isn't at a point yet where any of these blood tests are truly reliable, said Dr. Joel Salinas, a clinical assistant professor of neurology at NYU Langone Health in New York City.

“I wouldn't underestimate the length of that step” in translating the tau test to blood samples, said Salinas, who reviewed the studies. “There are sometimes issues with the amount of these proteins that can be found in the cerebrospinal fluid compared to the bloodstream. We can usually get kind of a sense of a parallel measure, but it's not the most direct measure, which is why there is yet to be a really good circulating biomarker for Alzheimer's disease, at least not one that everybody in the field feels very, very confident about.”

While better ones are now available, "they're certainly not to the level where people are using them very, very readily in clinical practice,” added Salinas, who is also chief medical officer for Isaac Health.

The advent of Alzheimer's drugs that remove amyloid beta from the brain makes the search for these sort of blood tests even more imperative, Griffin and Huber said.

Lecanemab (Leqembi) recently became the first such drug to receive full approval from the U.S. Food and Drug Administration, but patients taking the drug are required to undergo regular imaging scans to chart their progress.

“These new findings are timely and important with the recent approvals of Alzheimer's treatments targeting amyloid-beta, where confirmation of amyloid buildup and biomarker monitoring are required to receive treatment,” Griffin said. “While further standardization and validation are needed, blood tests may soon be one piece of the diagnostic workup in everyday practice.”

Findings that are presented at medical meetings and not yet published in a peer-reviewed journal are considered preliminary.

More information

The Alzheimer's Association has more about how Alzheimer's is diagnosed.

SOURCES: Hanna Huber, PhD, postdoctoral researcher in neurochemistry, University of Gothenburg, Sweden; Percy Griffin, PhD, director, scientific engagement, Alzheimer's Association, Chicago; Randall Bateman, MD, professor, neurology, Washington University School of Medicine in St. Louis; Joel Salinas, MD, clinical assistant professor, neurology, NYU Langone Health, New York City; presentations, Alzheimer's Association International Conference, Amsterdam, Netherlands, July 16-20, 2023; Nature Medicine, July 13, 2023