Bar-Ilan Helps Scientists See an Early Sign of Alzheimer’s That Current Tests Often Miss

Bar-Ilan Technology Helps Scientists See an Early Sign of Alzheimer’s That Current Tests Often Miss

A Hidden Stage of Alzheimer’s Disease

Alzheimer’s disease does not begin when memory problems first appear. In many cases, the disease may start developing silently in the brain years, and even decades, before a person or their family notices any symptoms.

One of the biggest challenges for scientists is that some of the earliest harmful changes in the brain are extremely difficult to see. Current diagnostic tools are mainly designed to detect large amyloid plaques, which are protein deposits that build up in the brains of many Alzheimer’s patients. But researchers believe that much smaller clusters of the same protein may appear earlier and may be especially toxic to brain cells.

These tiny clusters are called amyloid-beta oligomers. They are so small and elusive that today’s clinical imaging tools often miss them.

Bar-Ilan Technology That Helps Researchers See the Invisible

A technology developed by Prof. Shai Rahimipour of Bar-Ilan University’s Department of Chemistry is helping change that.

Prof. Rahimipour and his team developed a unique family of small ring-shaped molecules, known as cyclic peptides, that can recognize and bind to amyloid-beta oligomers while largely ignoring the larger amyloid plaques. When these molecules are tagged with fluorescent markers or radioactive copper, they allow researchers to “see” these hidden toxic clusters in brain tissue.

An International Study on the Earliest Brain Changes

The technology played a central role in a new international study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The study was led by researchers at the Icahn School of Medicine at Mount Sinai in New York, together with collaborators from Bar-Ilan University and Canada.

In the study, the researchers used a special mouse model that develops soluble amyloid-beta oligomers without forming the larger plaques usually associated with Alzheimer’s disease. Using Prof. Rahimipour’s molecular probes, the team was able to identify and study these hard-to-detect protein clusters.

How the Toxic Protein Clusters Harm Brain Cells

The findings showed that the oligomers can harm brain cells very early in the disease process. They disrupt the mitochondria, the tiny power stations that provide energy to nerve cells, and they interfere with communication between neurons, even before clear signs of inflammation appear.

“Our goal has always been to develop tools that detect the forms of amyloid-beta most closely associated with the earliest stages of Alzheimer’s disease,” said Prof. Rahimipour. “This study demonstrates how our technology can help reveal disease mechanisms that have remained hidden because existing diagnostic tools simply cannot see these toxic oligomers.”

Why Earlier Detection Could Matter for Treatment

The discovery could have important implications for the future of Alzheimer’s diagnosis and treatment. Recently approved anti-amyloid treatments, including Lecanemab and Donanemab, are currently monitored mainly through biomarkers related to amyloid plaques. But if toxic oligomers appear earlier, and possibly remain even after plaques are reduced, then being able to detect them directly could give doctors and researchers a clearer picture of how the disease is progressing and whether a treatment is truly working.

Earlier detection could also help identify patients during the silent phase of the disease, before symptoms begin. This may eventually make it possible to intervene earlier, select patients more accurately for clinical trials, and develop more sensitive ways to test new therapies.

From Bar-Ilan Research to Clinical Application

Prof. Rahimipour’s technology is now moving toward clinical application. Together with his team, he co-founded ApexBio, a startup developing the cyclic peptide platform for both diagnostic and therapeutic uses in Alzheimer’s disease. The company is conducting advanced preclinical studies, with the goal of entering first-in-human Phase 1 clinical trials, and is currently raising a second round of funding to accelerate development.

The technology has also been adopted by multiple research laboratories across North America, reflecting growing international interest in amyloid-beta oligomers as one of the most promising frontiers in Alzheimer’s research.

By helping scientists see what was previously hidden, Bar-Ilan-developed technology may bring the field one step closer to understanding Alzheimer’s at its earliest stages — and one day, to diagnosing and treating it sooner.