A new blood test can identify a hidden toxin that causes Alzheimer’s years before symptoms such as memory loss or confusion appear. It could considerably speed up the diagnosis if further tested and scaled up.
To detect the onset of Alzheimer’s years before any signs of cognitive impairment manifest, researchers have created a novel laboratory test that measures levels of a “toxic” protein. According to the research published in Proceedings of the National Academy of Sciences, the results could help identify people at risk for the disease and assist in developing early treatments for the condition.
What led to the development of the SOBA test?
The novel blood test, developed by researchers at the University of Washington (UW), detects a molecular precursor in the blood that can lead to the abnormal folding and clumping of proteins and the formation of amyloid beta (Aβ) plaques in the brain.
Although Aβ plaques are a well-known indicator of Alzheimer’s disease, it is unclear how they affect cognitive loss. Traditionally, scientists have considered these extracellular plaques as an early initiator of neuron malfunction and loss, which ultimately causes cognitive decline.
However, according to new research, only one-third of Alzheimer’s patients have these plaques, and occasionally, persons without cognitive impairments also have them in their brains. In other words, extracellular A plaques in the brain may not be essentially toxic by themselves, but they might derive from molecular toxins that are notoriously difficult to detect.
In essence, these toxins are the functional forms of the A present inside cells. Some researchers believe these “toxic A oligomers” can inadvertently damage neurons from afar, making them more susceptible to extracellular plaques and clumps.
Although the specifics are still unknown, the theory prompted UW researchers to develop the remarkably precise soluble oligomer binding assay or SOBA.
SOBA employs a unique synthetic test surface that can bind to proteins in the blood, allowing it to detect the presence of toxic oligomers.
SOBA can predict who currently has Alzheimer’s and who might get it later
Researchers discovered that the soluble oligomer binding assay, or SOBA, could find oligomers in the blood of Alzheimer’s patients. About eleven participants had oligomers in the control group, which only consisted of individuals who displayed no symptoms of cognitive impairment at the time of taking blood samples.
Ten of those individuals were able to receive medical attention, and all of them later received a diagnosis of moderate cognitive impairment (MCI) or brain pathology associated with Alzheimer’s. Before any symptoms appeared, the test had already identified those at risk, and the toxic oligomers were missing from the blood samples of those who never went on to have cognitive impairment.
In another assessment of the test, researchers collected blood samples from 310 research participants who had previously provided blood samples and some of their medical information for Alzheimer’s research. The subjects did not exhibit any symptoms of dementia, Alzheimer’s, moderate cognitive impairment, or any other type of cognitive impairment at the time the blood samples were obtained.
SOBA discovered oligomers in the blood of people with MCI and moderate to severe Alzheimer’s. Researchers examined the brains of 53 participants via autopsy after they died and found toxic oligomers in the blood samples of 52 of those cases. The blood samples were taken years before their deaths.
Researchers hope to make tests widely accessible and affordable.
To transform SOBA into an oligomer diagnostic test, the research team is collaborating with researchers at AltPep, a UW spinout firm.
Dr. Daggett, one of the researchers, has stated that they desire a method that can identify Alzheimer’s in the best-case scenario without requiring lumbar punctures or costly imaging procedures. Besides, the test appears to be much more sensitive and specific than other testing methods.
Instead of requiring costly technology and processing, she claimed that SOBA only needs a standard, straightforward blood test that is inexpensively available at most labs, even in a doctor’s office. She added that the price range for various operations is $5,000 to $8,000.
She also stated that this is just the beginning and that they are further working to validate the results.
SOBA Could Be Used to Identify Other Disorders, Such as Type 2 Diabetes and Parkinson’s
Dr. Daggett has stated that the FDA has approved their breakthrough status application to develop this test.
According to researchers, the test has further potential because it is theoretically possible to detect other amyloid illnesses using the same technology. Misfolding proteins appear to be associated with Parkinson’s disease, type II diabetes, and Lewy body dementia, suggesting that SOBA could one day be modified to detect early signs of these other diseases.
References
- Shea, D., Colasurdo, E., Smith, A., Paschall, C., Jayadev, S., Keene, C.D., Galasko, D., Ko, A., Li, G., Peskind, E. and Daggett, V., 2022. SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers. Proceedings of the National Academy of Sciences, 119(50), p.e2213157119.
- Neff, R.A., Wang, M., Vatansever, S., Guo, L., Ming, C., Wang, Q., Wang, E., Horgusluoglu-Moloch, E., Song, W.M., Li, A. and Castranio, E.L., 2021. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Science advances, 7(2), p.eabb5398.
- Upham, B., New Blood Test Can Identify Toxic Protein Years Before Alzheimer’s Symptoms Appear. Everyday Health. https://www.everydayhealth.com/alzheimers-disease/new-blood-test-can-identify-toxic-protein-years-before-alzheimers-symptoms-appear/. Accessed: 4th Jan, 2023.
- Cassela, C., New Blood Test Accurately Predicts Alzheimer’s Years Ahead of First Symptoms. Science Alert. https://www.sciencealert.com/new-blood-test-accurately-predicts-alzheimers-years-ahead-of-first-symptoms. Accessed: 4th Jan, 2023.