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• Alzheimer’s disease is the most common form of dementia, and the number of people with the condition is increasing rapidly.
• Treatment is most effective if started in the early stages, so research is focusing on early diagnosis.
• Scientists can detect biomarkers for Alzheimer’s disease in cerebrospinal fluid (CSF), but CSF sampling involves a lumbar puncture that can be distressing and take several days to recover from.
• Now, a study has detected Alzheimer’s disease biomarkers in the blood, potentially leading to easier, earlier tests for Alzheimer’s disease.

Dementia currently affects around 60 million people worldwide, and the number is projected to rise to more than 150 million by 2050. Alzheimer’s disease, the most common form of dementia, causes 60-80% of cases.

Available treatments work to relieve the symptoms, which may include:

• memory loss: problems taking in and remembering information
• cognitive deficits: difficulty with reasoning, complex tasks, and judgment
• problems recognising people or things
• problems with spatial awareness
• difficulty speaking, reading, or writing
• personality or behavior changes.

Important to diagnose Alzheimer’s early

Alzheimer’s disease is characterized by amyloid plaques and tau tangles in the brain, which researchers believe cause symptoms by interfering with the function of nerve cells.

Newer disease-modifying treatments, the monoclonal antibodies lecanemab, donanemab and aducanumab, demonstrably clear plaque build-up, and may help slow down cognitive decline.

These treatments are most effective if undertaken early in the course of the disease. Scientists searching for ways to diagnose Alzheimer’s disease early have found biomarkers in cerebrospinal fluid (CSF) that indicate the disease.

However, to sample CSF a clinician must perform a lumbar puncture, an invasive procedure that involves inserting a needle into the spine.

New research from The Global Alzheimer’s Platform Foundation has suggested that these biomarkers can also be detected in blood samples.

The research, which appears in Alzheimer’s & Dementia, the journal of the Alzheimer’s Association, suggests this may lead to simpler, earlier tests for Alzheimer’s disease.

Dr. Heather M. Snyder, Ph.D., vice president of Medical and Scientific Relations at the Alzheimer’s Association, which published the study, explained to Medical News Today:

“Blood tests are simpler, less invasive, less expensive and more accessible than imaging scans and spinal taps, which makes their use in research — and eventually in the doctor’s office — very attractive. And they have the potential to be very valuable tools for engaging more diverse populations in Alzheimer’s research.”

“That said,” she continued, “the current Alzheimer’s blood biomarker tests are not yet FDA [Food and Drug Administration] approved. Without that rigorous review, the marketing claims and news coverage are generating confusion.”

How researchers can detect Alzheimer’s in fluid samples

CSF is the fluid that surrounds the brain and spinal cord, so it contains proteins that serve as biomarkers for changes in the brain.

Research shows that biomarkers linked to beta-amyloid and tau are present in the CSF of people with mild cognitive impairment and early Alzheimer’s disease, as well as in those with the later-stage disease.

People who go on to develop Alzheimer’s disease may have decreased levels of beta-amyloid-42 in their CSF long before they show symptoms. This is linked to the build-up of amyloid plaques in the brain — as amyloid is deposited in the brain, the level of soluble beta-amyloid-42 in the CSF decreases.

Conversely, increased levels of tau protein in CSF are associated with Alzheimer’s disease development. Research suggests that tau levels increase not only during neurodegeneration later in Alzheimer’s disease progression, but may happen before symptoms of the disease are noticed.

Researchers devise a blood biomarker test

Participants in the recent study were aged between 60 and 85 years. The majority were non-Hispanic white, but there were smaller groups of Hispanic, non-Hispanic Black and other ethnicities.

The researchers divided them into three groups:

• cognitively healthy — no self- or partner-reported memory loss or concerns
• mild cognitive impairment — minimal to mild functional impairment but with preservation of independence in functional abilities, or a diagnosis of mild cognitive impairment based on the National Institute on Aging (NIA)-Alzheimer’s Association (AA) criteria
• mild Alzheimer’s disease — a diagnosis of probable Alzheimer’s disease based on the NIA-AA criteria, or screening results conforming to mild Alzheimer’s.

All participants made three visits to the laboratory. On the first, they underwent cognitive testing and blood sampling; the second was for PET scans to assess amyloid in the brain — or CSF sampling where this was unavailable. On the third visit they underwent more blood sampling.

The researchers found no relationship between beta-amyloid–40 or t-tau in the blood and amyloid positivity from PET scans. However, there were strong relationships between blood levels of beta-amyloid–42, p-tau181, p-tau217, and amyloid positivity.

The researchers recorded lower values of beta-amyloid-42, and higher values for p-tau181 and p-tau217, across all three groups for those whose PET scans showed amyloid.

The average concentration of all three biomarkers was significantly less for non-Hispanic Black participants than for non-Hispanic white participants.

“[This study] suggests that p-tau217, p-tau181 and [beta-amyloid-42/beta-amyloid-40] ratio were significant predictors of amyloid positivity in all three race and ethnic groups in the study population. This is consistent with what we have seen in other studies, and adds to our understanding of the potential utility of Alzheimer’s blood tests.”

– Dr. Heather Snyder

Could blood biomarkers be a diagnostic tool for Alzheimer’s?

Dr. Clifford Segil, D.O., neurologist at Providence Saint John’s Health Center in Santa Monica, CA, does not believe that blood tests can be used to diagnose Alzheimer’s disease:

“There is no clinical usefulness of using a blood test to determine if [it] correlates with brain amyloid burden as there is no clear correlation between high amyloid brain burden and cognitive issues. Many patients with severe memory loss have low brain amyloid and many patients with no memory loss have high amyloid brain deposits.”

However, Dr. Snyder was more positive.

“There is a growing body of evidence — published in the scientific literature, with more to be reported in July at the Alzheimer’s Association International Conference (AAIC) in Philadelphia — that certain blood-based Alzheimer’s disease biomarkers are essentially equivalent with detection methods in cerebrospinal fluid (CSF) and imaging (PET, MRI),” she told us.

So, not a replacement for the range of other tests needed for a confirmed Alzheimer’s diagnosis, but perhaps a simple blood test could highlight the need for further investigation in people who are showing symptoms that might indicate Alzheimer’s disease.

Finally, Dr. Emer MacSweeney, CEO and Consultant Neuroradiologist at Re:Cognition Health, not involved in this study, expressed optimism about the future potential of this research, saying:

“This study represents a pivotal advancement, offering crucial insights and paving the way for faster and more accurate Alzheimer’s diagnosis, which is imperative for treating the disease with new-generation medications.”