Blood tests for Alzheimer’s: a hit or a miss?

Photo/Elena Resko
Alzheimer's blood tests

Doctor’s typically diagnose Alzheimer’s with the help of brain imaging and cognitive tests, along with taking a patient’s medical history into account. But lately, blood tests are gaining recognition for its ability to rule out other potential causes of memory loss, and to diagnose Alzheimer’s more quickly.

With American healthcare company Labcorp launching its trio of blood biomarkers only last month, these tools can signal the need for more advanced tests for diagnosing the neurodegenerative disease. 

These tests are based on the identification of specific biomarkers that are associated with the pathological changes in the brain, such as the accumulation of amyloid-beta and tau proteins, which are hallmarks of Alzheimer’s disease, according to Dung Trinh, chief medical officer of Healthy Brain Clinic in the U.S..

How are blood biomarker tests for Alzheimer’s different from other diagnostic measures?

In the case of amyloid beta being used as a blood biomarker, Trinh explained that the blood test focuses on the ratio of different forms of amyloid-beta – A-beta 42 and A-beta 40 – that indicates the formation of amyloid plaques in the brain. Whereas, with tau proteins, elevated levels of it lead to its accumulation forming neurofibrillary tangles, which harms the communication between neurons. Other ways to measure neurodegeneration include using neurofilament light chains (NfLs) – proteins found in cerebrospinal fluid – as biomarkers, which are associated with neuron damage, and therefore, the loss of brain functioning. 

While the exact mechanism behind blood tests for Alzheimer’s is not fully understood, Trinh pointed out that these markers provide information on the presence of Alzheimer’s-related brain changes. The perks of these markers are three-fold, where the tests may be used as surrogate endpoints – which measures how effective a treatment is – in clinical trials, which could potentially shorten the duration and size of trials, according to Trinh. He added that this could also aid in identifying those who are most likely to benefit from specific treatments.

But what makes these tests really stand out is how different they are from current diagnostic tools like positron emission tomography (PET) scans and cerebrospinal fluid (CSF) analysis. A CSF analysis typically involves a lumbar puncture, where a hollow needle is inserted into the spinal cord in order to extract the CSF. As this process is rather invasive and may lead to side effects like nausea, headaches and even the risk of infection, a blood test eliminates these potential side effects from occurring.

Besides, measures like PET tracers, which had soon become a hit at clinics because of their ability to observe brain function when paired with a magnetic resonance imaging (MRI) scan, are starkly expensive when compared to blood tests. The out-of-pocket cost of one of these tests is $3000, which isn’t discounted under most private insurances in the U.S, making it a financial burden on many.

Moreover, Alessio Travaglia, director of Neuroscience at the Foundation for the National Institutes of Health (FNIH) – an independent nonprofit organization that supports the National Institutes of Health (NIH) in the U.S. – explained that while PET scans allow the detection of cognitive impairment in real time, there is a need for a cheaper and quicker alternative.

“The reason why there was the need to develop something like a blood biomarker is that, as you can imagine, it’s much easier to go to any clinic; they draw some blood and they can measure at the same time, glucose, lipid, enzymes and biomarkers related to Alzheimer’s disease… So, comparing all the assays could be helpful to correlate changes in the brain,” said Travaglia, who is directing a research program on blood biomarkers for Alzheimer’s.

Labcorp’s trio of blood biomarker tests enter hospitals, FNIH makes progress in Alzheimer’s research

Although Labcorp’s triple biomarker tests, which were rolled out in hospitals in the U.S. in October, do not make for a clear-cut diagnosis, they are a convenient way for doctors to determine the changes in the brain in people who may have the disease, thereby speeding up further diagnosis and to navigate treatment care quicker. 

The tests comprise a beta-amyloid ratio test, where the amount of amyloid protein is measured in the blood. The second detects tau and the third looks for NfL in the blood, as an abundance of these proteins may be indicative of Alzheimer’s. The NfL test set foot into the market last year, and is used to detect signs of other neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), dementia, concussions and Parkinson’s disease, as well.

Labcorp is among various other test makers devoted to Alzheimer’s research. Travaglia’s team at the FNIH is working to bring U.S. Food and Drug Administration (FDA)-approved Alzheimer’s tests to the clinic. Unlike with PET tracers, the FNIH aims to create tests that can predict whether a person will develop Alzheimer’s prior to them experiencing symptoms of the disease. 

“Imagine that earlier on, you can know that you will develop Alzheimer’s in several years, and you can start making changes in your lifestyle; There are proven lifestyle changes that can affect the trajectory of Alzheimer’s disease,” said Travaglia.

This could help doctors flag the disease ahead of time and ensure that people are able to take preventative measures against the development of the disease. Moreover, the researchers at the institute are attempting to build tests that can track disease progression.  

“Understanding where in the disease a patient is (with regards to stages of disease progression in Alzheimer’s), it is important not just from a pure academic perspective, because it’s scientifically interesting, but also to see whether a patient is responsive to a specific drug,” he said. 

This way doctors can correlate therapeutic effects with how the disease continues to manifest in a patient, and figure out how well certain drugs work.

PharmaKure proves itself in Alzheimer’s clinical trials

Meanwhile, British spinout of The University of Manchester, PharmaKure has also come up with its blood biomarker test to detect cognitive decline. The ALZmetrix blood test is steadily proving its worth in clinical trials. A study tested the blood of 54 participants who had previously undergone either a PET scan or CSF analysis. The trial found that ALZmetrix was capable of determining the presence of amyloid deposits in the brain as well as predicting how far along the path towards Alzheimer’s disease a patient was.

In a press release, Farid Khan, chief executive officer at PharmaKure Limited mentioned that blood tests addressed a major unmet need for an alternative to current diagnostic methods. 

Khan said: “This study has demonstrated how to get early warning signs of cognitive decline using whole blood. We will be using the exciting data to expand our ALZmetrix test to additional patients and new biomarkers.”

This peak in blood biomarker research in neurodegenerative diseases did not just begin in the past month. Earlier this year, American company Quest Diagnostics broke into the Alzheimer’s diagnostics space with its direct-to-consumer blood test. The $399 test known as AD-Detect, detects amyloid levels in the blood, particularly the ratio of A-beta 42 and A-beta 40 biomarkers. 

By purchasing the test online, people are able to send these test results to a doctor who can decide on the next steps in confirming a diagnosis. While this test has not been FDA-approved, it is currently being used by doctors in the U.S..

Concerns over accuracy and other drawbacks

However, Travaglia voiced his concern over tests that have not been given the go-ahead from the FDA. As certain tests are sold online despite the lack of peer-reviewed data to back them, this could pose a threat to an accurate diagnosis.

“We want to build trust in society. And when we’re selling a product that we don’t know whether it’s going to work or not, that’s a big problem,” said Travaglia.

Furthermore, this could be dangerous for someone who assumes that the test works well, and to self-diagnose based on possibly false results. Although these tests are offered at a fee much cheaper than other diagnostic standards – for example, a PET scan is 10 times more expensive than PharmaKure’s online-available test – it doesn’t guarantee an error-free result. In fact, some people may receive false positive or false negative results, which leads to diagnostic uncertainty.

Besides, the accuracy of blood tests for Alzheimer’s disease varies depending on the specific biomarker, the assay, and the study, according to Trinh. 

Trinh said: “Some blood tests have demonstrated good sensitivity and specificity, but they may not yet match the precision of PET scans or CSF analysis. The accuracy of these tests is a subject of ongoing research.”

And that’s not all. Trinh explained that not only would the accuracy and consistency of these tests vary from lab-to-lab but also that the interpretation of results may be complex, especially since we’re dealing with multiple biomarkers tied together. Plus, the complexity of the disease in itself could deter blood tests from capturing the full spectrum of pathological changes.

Diagnosing Alzheimer’s: upcoming projects 

Nevertheless, this doesn’t stop researchers from looking for ways to expand diagnostic options. The team at FNIH is working on a project measuring synaptic health. Synapses form the junction between two nerve cells, and their damage has been linked to Alzheimer’s and other forms of dementia. 

By validating a protein called synaptic vesicle 2A (SV2A) as a potential biomarker, it could offer further insight into diagnosing Alzheimer’s.

“This is something, I think, that is quite exciting. And the other thing that is exciting, is developing an Alzheimer biosignature; there is not just A (amyloid) beta, there is not just tau, there is not just SV2A. There are so many other things,” said Travaglia, who added that a biosignature could lay the groundwork for personalized medicine in Alzheimer’s care. 

While Trinh remarks that we need to be mindful that these tests are still in the research and validation phase, he believes that as “they become more accurate and reliable, they have the potential to revolutionize the diagnosis and treatment of Alzheimer’s disease, offering hope for both patients and healthcare providers.”

Mirroring these thoughts, Travaglia compared how blood pressure became one of the key indicators that dictated heart and vessel health, to what blood biomarkers could potentially be for neurodegenerative diseases.

“The way I see it is that blood biomarkers, they may not be helping people with disease today, rather than changing their lifestyle intervention, but certainly helps to develop other treatment options. So, I’m really excited about all of these changes, and the fact that it is moving so fast,” said Travaglia.

Although more research is needed to bring this tool to the frontlines, there is burgeoning interest in the field, reflected in breakthrough Alzheimer’s drug Leqembi receiving the thumbs up from the FDA in January. So, these advances may be making way for quicker diagnostic and treatment approaches ahead. 

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