Can an Alzheimer’s blood test help early diagnosis of the disease?

In 2023, controversy reigned over the FDA’s decision to approve aducanumab and lecanemab, due to a lack of evidence for their efficacy. One of the limitations of the trials of these drugs had been the inability to start their use earlier in the progression of the disease, potentially affecting results, it was argued at the time.

Early diagnosis could reduce healthcare costs overall as, even if it were not possible to treat Alzheimer’s disease, it would help to manage other chronic conditions and reduce hospitalizations better. The CDC estimates up to $64,000 could be saved per person with dementia, with early diagnosis.

Dr. David Hunter, an assistant professor of neurology with McGovern Medical School at UTHealth Houston, told Medical News Today in an email that more tools to detect Alzheimer’s disease would be welcomed:

“As Alzheimer’s specialists, we very much want a blood test that confirms the diagnosis. This has become urgent in the last year, as there is now an FDA-approved drug for Alzheimer’s that we call a Disease Modifying Therapy (DMT). At the moment, we rely on either a PET scan or a Lumbar Puncture. Both are expensive and somewhat invasive tests.”

The hunt has been on for a simple blood test or saliva test that could determine whether or not somebody has the characteristic buildup of amyloid beta and tau in the brain. One of the challenges posed by developing a blood test is that the blood-brain barrier limits the amount of substances present in the brain from reaching the bloodstream. Plus, tau and amyloid proteins are, by their nature, sticky.

There has been significant research into determining the form of tau found in the blood that is the most likely to indicate raised levels of tau and amyloid in the brain, and not elsewhere in the body. Previous research has looked at the ratio of certain forms of amyloid beta compared to other forms, and p-tau217 has also emerged as a form of tau that is indicative of the development of amyloid and tau buildup in the brain.

In 2023, a blood test for detecting amyloid beta protein was developed and made available by a company called AD-Detect. They also created the ALZpath pTau217 assay, which is only available to researchers but allows them to detect this form of tau in a blood test.

This was made available, free of charge, to an international group of researchers based across Scandinavia, Europe, and the United States to determine how this assay compared to using cerebrospinal fluid to biomarkers used to detect Alzheimer’s disease.

Researchers looked at data from three sources — a cohort of individuals at risk of Alzheimer’s disease — and the other two were biobanks set up to investigate neurodegenerative conditions or aging and dementia. There were a total of 786 participants with a mean age of 66, including 504 female and 282 male participants.

Analysis of data showed that the assay was able to identify individuals in which there were abnormal levels of amyloid beta and tau but did not look at whether or not this correlated with the incidence of Alzheimer’s disease. Researchers tested the assay in conjunction with imaging data.

They found that the assay provided more accurate detection of hippocampal atrophy and was similar in its ability to detect abnormal levels of amyloid beta and tau as cerebrospinal fluid tests. This was the case across the three groups.

The authors said that the assay could detect abnormal levels of amyloid beta and tau in 80% of tested participants and that the remaining 20% would need confirmatory imaging or cerebrospinal fluid tests. They claimed this was more accurate than current diagnostic tools and could be used to identify people for early intervention with emerging pharmaceutical treatments designed to reduce amyloid buildup.

The makers of the assay reviewed the manuscript before it was submitted to the journal.

Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the research, told MNT that a blood test was not necessarily the answer for early detection. Dr. Segil said: “The authors noted there is no clear relationship to serum tau protein levels and cognitive complaints and therefore has no clinical utility for a neurologist or any physician to evaluate a patient with memory loss in 2024.”

“I strongly disagree, as a clinical neurologist who diagnoses and treats patients with cognitive complaints and memory loss, that blood biomarkers have any role in the clinical evaluation of patients with memory loss and dementia and would agree these may have a role in pharmaceutical drug trial enrollment as proposed by this paper.

[T]he goal to reduce Alzheimer’s diagnoses on advanced confirmatory tests is a pharmaceutical company goal and not a neurologist’s goal.”

– Dr. Segil

He warned there were risks with the approach proposed:

“If biomarkers are used millions of people will be diagnosed with Alzheimer’s Disease who may have no memory loss or cognitive impairment. A blood test for tau has no place to be used in a primary care physician’s office or a neurologist’s office in the clinical evaluation of patients with memory loss or cognitive impairment being evaluated for Alzheimer’s dementia. It will diagnose patients with Alzheimer’s dementia who are without memory loss and may never have memory loss.”