In a proof-of-concept study, the test successfully identified five critical biomarkers associated with Alzheimer’s disease, exceeding the capabilities of currently available commercial blood tests.
Researchers at the Keck School of Medicine of USC have created a new blood test that could make it easier to detect Alzheimer’s disease early. This innovative tool, called the Penta-Plex Alzheimer’s Disease Capture Sandwich Immunoassay (5ADCSI), measures five key proteins linked to Alzheimer’s in a single test. That’s more than most current tests, and it runs on equipment already found in many labs, making it much more accessible.
The findings were published in the Journal of Alzheimer’s Disease and backed by the National Institutes of Health. Scientists have long known that certain proteins, such as amyloid and tau, build up in the brain as Alzheimer’s progresses. These same proteins also show up in the blood, giving researchers a window into the disease’s early stages. Detecting them early could allow doctors to intervene before serious memory loss begins.
While other tests do exist, many are expensive, require specialized tools, and only look at one or two markers at a time. The 5ADCSI test stands out because it tracks five critical biomarkers at once. It uses xMAP® technology, a widely used platform developed by the biotechnology company Luminex.
“The biggest advantage is that our test is very cost-effective compared to other existing technologies, and it’s relatively easy to implement because many laboratories in universities, hospitals, and clinics are already using this technology,” said Ebrahim Zandi, PhD, associate professor of molecular microbiology and immunology at the Keck School of Medicine, who led the research.
Creating a low-cost test is critical because it could bring widespread annual screenings for Alzheimer’s disease within reach. Like cholesterol and blood sugar tests, 5ADCSI could identify patients who may benefit from medication or lifestyle changes, such as increased exercise, to prevent or slow Alzheimer’s.
“In the 10 to 20 years Alzheimer’s takes to develop, proteins such as amyloid and tau are slowly building up,” Zandi said. “If we have an affordable blood test that detects those proteins early on, we can start interventions long before symptoms begin.”
Building the blood test
To create the 5ADCSI test, the researchers first selected a series of biomarkers known to build up in Alzheimer’s disease: two types of amyloid (Aβ40 and Aβ42), phosphorylated tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).
They developed a custom test to detect the presence of those biomarkers in a blood sample using the xMAP® technology. This method uses tiny color-coded beads coated with antibodies that bind to specific biomarkers. When a blood sample is added, the biomarkers in the sample bind to the beads. Powerful imaging sensors then detect the colors emitted from the beads in order to measure the biomarkers.
Once the test was built, researchers used it to measure Alzheimer’s-associated biomarkers in 63 blood samples across three groups: 11 patients with Alzheimer’s disease, 17 patients with mild cognitive impairment (a precursor of Alzheimer’s), and 35 healthy participants.
The 5ADCSI test detected the highest levels of the biomarkers in patients with Alzheimer’s disease, followed by those with mild cognitive impairment. One biomarker in particular, p217Tau, showed a very strong correlation with the condition.
Researchers then used the same test to measure biomarkers in cerebrospinal fluid (CSF), which typically contains higher levels of Alzheimer’s-associated proteins but is harder and more expensive to collect. They found moderate to strong correlations between blood and CSF results, suggesting the blood test is sensitive enough for early detection of the proteins.
From research tool to clinical test
The 5ADCSI test started as a research solution to a practical problem. Christopher Beam, PhD, associate professor of psychology at the USC Dornsife College of Letters, Arts, and Sciences, needed a more affordable way to measure Alzheimer’s biomarkers for his studies on cognitive aging. Zandi provided a solution in the form of 5ADCSI.
Now, the team is working to develop the technology and prove that it can work as a measurement tool in the clinic. To build on the proof-of-concept study, the researchers plan to test 5ADCSI’s accuracy with several hundred patients across different stages of Alzheimer’s disease.
Zandi envisions widespread use of the test, especially because it relies on technology that is affordable and widely available, even outside the U.S. His long-term goal is to create a brain health risk assessment that pairs 5ADCSI with genetic testing for APOE4, the gene variant linked to Alzheimer’s disease, to help people understand their personal risk for the condition.
Reference: “High precision and cost-effective multiplex quantification of amyloid-β40, amyloid-β42, p181Tau, p217Tau, neurofilament light chain, and glial fibrillary acidic protein from plasma and serum” by Farshad Alishahi, Christopher R Beam, Margaret Gatz, Lon S Schneider, Daniel A Nation, Hussein N Yassine, Hillard Kaplan, Suchita Ganesan, Ioannis Pappas, Deborah Winders Davis and Ebrahim Zandi, 23 December 2024, Journal of Alzheimer’s Disease.
DOI: 10.1177/13872877251340999
This work was supported by the National Institutes of Health [R01 AG063949, R01 AG060049, R01 AG054442, RF1 AG054442].
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.