Early Alzheimer's Diagnosis May Be Closer With New 5-in-1 Blood Test

Scientists have developed a new blood test that can detect signs of Alzheimer’s disease in a simple, inexpensive and accurate way. The test measures six proteins linked to the disease and has shown good results when compared to more complex tests, such as spinal fluid. This new tool could make it easier to diagnose Alzheimer’s disease early on a large scale, helping more people receive treatment and follow-up in a timely manner.

Alzheimer’s disease is the most common cause of dementia and mainly affects memory and the ability to think clearly. Currently, the most accurate methods of detecting Alzheimer’s involve expensive tests or uncomfortable procedures, such as a spinal tap (to collect spinal fluid) or sophisticated brain imaging.

That’s why scientists are looking for ways to use simple blood tests to identify early signs of the disease. This would make diagnosis more accessible to more people and could help start treatment sooner.

A study, conducted by researchers at the University of Southern California, USA, aimed to create a new type of blood test, called 5ADCSI, that can detect specific proteins linked to Alzheimer’s.

These proteins, called biomarkers, appear in the blood when the brain begins to undergo changes characteristic of the disease. The test is designed to measure six biomarkers at once:

1. Aβ40 and Aβ42, which are linked to plaque buildup in the brain;

   
   

2. Tau p181 and Tau p217, forms of a protein that becomes toxic when it undergoes chemical changes and builds up inside neurons;

   
   

3. NfL, which indicates nerve cell damage;

   
   

4. GFAP, a protein linked to inflammation in the brain.

   
   

To create this test, researchers used a technology called Luminex xMAP, which works as a type of “smart protein reader.” This technology uses tiny colored spheres, each coated with a specific “capture,” like little traps that only catch the right biomarker.

When these spheres are mixed with the person’s blood, each biomarker attaches itself to its corresponding sphere. Then, a device reads these spheres and calculates the amount of each biomarker present in the blood.

In addition, scientists used commercial antibodies, which are ready-made substances available on the market that recognize and bind specifically to these Alzheimer’s proteins. This makes it easier to use the test in regular laboratories, without the need for very sophisticated or exclusive equipment.

To see how well the test worked, the researchers tested the 5ADCSI on blood (plasma or serum) and cerebrospinal fluid (CSF), the fluid that surrounds the brain, from 63 people: 35 with normal brain function, 17 with mild cognitive impairment (a risk factor for developing Alzheimer’s), and 11 with a confirmed diagnosis of Alzheimer’s.

The results were very positive. The test was able to measure biomarkers with high accuracy and showed good levels of agreement between blood and brain fluid. For example, the ratio of Aβ42 to Aβ40 in the blood correlated with 0.78 (on a scale of 0 to 1) with the same value in CSF, a high number that indicates that blood values ​​reflect well what is happening in the brain.

Furthermore, the test had an excellent ability to distinguish between those who had Alzheimer's and those who did not. For example, the biomarker p217Tau, measured in the blood, had an AUC index of 0.95 (on a scale of 0 to 1), which means that the test was almost perfect in correctly identifying cases of the disease.

This new test, the 5ADCSI, is a major breakthrough because it combines precision, low cost and easy access. Unlike other more expensive tests that are limited to specialized centers, it uses materials and equipment already found in many laboratories around the world.

This means that it can be used on a large scale, helping to detect Alzheimer's earlier, which is essential for planning treatment, offering adequate support to the person and their family, and even for including more people in research into new drugs.

READ MORE:

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

Farshad Alishahi, Christopher R Beam, Margaret Gatz, Lon S Schneider, Daniel A Nation, Hussei N Yassine, Hillard Kaplan, Suchita Ganesan, Ioannis Pappas, 

Deborah Winders Davis, and Ebrahim Zandi 

Journal of Alzheimer’s Disease. 2025;0(0)

https://doi.org/10.1177/13872877251340999

Abstract:

Current methods to quantify blood biomarkers for Alzheimer's disease (AD) are expensive and are not widely available. To develop a low-cost, sensitive, and accurate multiplex assay to quantify Aβ40, Aβ42, p181Tau, p217Tau, NfL, and GFAP biomarkers in plasma and serum based on a widely available technology. We used commercial antibodies to Aβ40, Aβ42, p181Tau, p217Tau, NfL, and GFAP, and xMAP Luminex technology, and developed the multiplex 5ADCSI to quantify these biomarkers from plasma and serum. The utility of 5ADCSI was tested in matched cerebrospinal fluid (CSF) and plasma or serum of a cohort of cognitively normal (CN: n = 35), with mild cognitive impairment (MCI: n = 17), and with AD (n = 11) individuals. The 5ADCSI demonstrated high specificity and sensitivity, with excellent precision. In clinical samples, moderate to strong correlation is observed between CSF and plasma or serum for Aβ42/40 (r = 0.78), p181Tau/Aβ42 (r = 0.57), p217Tau/Aβ42 (r = 0.72), p181Tau (r = 0.59), p217Tau (r = 0.75), and GFAP (r = 0.59). The AUC of receiver-operator characteristic curve for differentiating CN from AD for plasma/serum and CSF are 0.75, and 0.80 for Aβ42/40, 0.95, 0.91 for p217Tau, 0.76, 0.81 for p181Tau, and 0.73 and 0.78for GFAP, respectively. The 5ADCSI assay is highly specific, sensitive, and accurate. The wide availability of the base technology of 5ADCSI is an advantage over other similar methods and would allow cost-effective large-scale studies for validation of blood biomarkers for early diagnosis of AD.