New blood test detects Alzheimer’s years before symptoms

One of the most challenging aspects of Alzheimer’s disease is how difficult it is to diagnose in its early stages. Now, a new study by researchers at the University of Connecticut (UConn) has developed two rapid tests that can detect early biological markers of the disease.

The scientists say these innovative techniques could eventually allow doctors to identify a range of illnesses quickly and easily during routine appointments.

Detecting Alzheimer’s before symptoms emerge

Alzheimer’s disease is the most common cause of age-related dementia, accounting for between 60 and 80 percent of all cases. It typically begins with mild forgetfulness and confusion, but as it progresses, patients may struggle with essential functions such as swallowing and walking.

There is growing evidence that the disease begins many years before symptoms become clear – possibly as much as two decades earlier, according to the Alzheimer’s Association. However, there is currently no straightforward way to test for the condition in these early, silent stages.

Fast, low-cost testing technology

A team of UConn chemists, including Jim Rusling and Jessica Rouge, working with colleagues at the UConn Health Center on Aging, have now developed a rapid and affordable blood test that identifies Alzheimer’s disease markers. The test analyses a small sample of blood plasma using an array that recognises microRNA molecules associated with the disease.

The two tests combine several advanced technologies. At the heart of their approach is the CRISPR CAS13A system – part of a family of bacterial proteins best known for gene editing. CAS13A acts like molecular scissors, cutting up ribonucleic acid (RNA). When specific bits of RNA linked to Alzheimer’s processes are detected, CAS13A triggers a reaction that lights up a tiny dye molecule. The dye then glows, either through fluorescence or electrochemiluminescence.

High-tech design for precision detection

For the fluorescence-based test, the researchers created a tray containing 96 tiny wells using a specialised 3D-printed material designed to anchor molecules that hold CAS13A in place. Each molecule of CAS13A is attached to a strand of test RNA that precisely matches an Alzheimer’s RNA biomarker. When the biomarker binds to its complementary strand in the sample, CAS13A is activated to cut nearby RNA – including the RNA masking the dye. Once unmasked, the dye glows, revealing the presence of the Alzheimer’s marker.

A similar approach was applied to the electrochemiluminescence version, where a small array was developed to detect three RNA biomarkers simultaneously.

Aiming for a comprehensive diagnostic tool

“Over the long term, we’d like to come up with a single assay that could monitor multiple types of blood biomarkers for early Alzheimer’s,” says Dr Jim Rusling, professor at the Department of Chemistry at UConn.

The research team plan to continue collaborating with experts at UConn Health’s Center on Aging to test a larger number of patient samples and track them over time. Their goal is to determine how accurately the new tests can predict the development of Alzheimer’s disease in its earliest stages.