USC researchers develop low-cost blood test for early Alzheimer’s detection

Researchers from the Keck School of Medicine of USC have developed a blood test that can identify early signs of Alzheimer’s disease by measuring proteins linked to the condition. The new test, known as Penta-Plex Alzheimer’s Disease Capture Sandwich Immunoassay (5ADCSI), detects five biomarkers simultaneously, which is more than existing blood tests and runs on equipment commonly used in many laboratories. A proof-of-concept study, funded by the National Institutes of Health, was just published in the Journal of Alzheimer’s Disease.

Scientists have found several reliable blood-based biomarkers of Alzheimer’s disease. These proteins, including amyloid and tau, build up in the brain—and blood—as the disease progresses. A blood test for these proteins can help catch the disease in its earliest stages, when treatment might be able to prevent or or delay cognitive decline.

Several tests exist, but they are expensive, rely on specialized equipment and can only detect a few biomarkers at a time. By contrast, 5ADCSI can measure five key Alzheimer’s biomarkers and relies on xMAP^® technology, a widely available system from 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.

About this research

In addition to Zandi and Beam, the study’s other authors are Farshad Alishahi from the Department of Molecular Microbiology & Immunology and Norris Cancer Comprehensive Cancer Center, Keck School of Medicine of USC, University of Southern California; Lon S. Schneider and Hussein N. Yassine from the Department of Neurology, Keck School of Medicine of USC, University of Southern California; Suchita Ganesan and Ioannis Pappas from the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California; Margaret Gatz from the Center for Economic and Social Research, University of Southern California; Daniel A. Nation from the Leonard Davis School of Gerontology, University of Southern California; Hillard Kaplan from the Economic Science Institute, Chapman University, Orange, California; and Deborah Winders Davis from the University of Louisville School of Medicine, Louisville, Kentucky.

This work was supported by National Institutes of Health [R01 AG063949, R01 AG060049, R01 AG054442, RF1 AG054442].