A molecular imaging technology developed by Prof. Shai Rahimipour of Bar-Ilan University is helping scientists uncover one of the earliest and most elusive drivers of Alzheimer's disease, opening new possibilities for earlier diagnosis and more precise treatment.
The technology played a central role in a new international study published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association , led by researchers at the Icahn School of Medicine at Mount Sinai in New York together with collaborators from Bar-Ilan University and Canada. The study provides compelling evidence that soluble amyloid-beta oligomers -- tiny toxic protein aggregates believed to trigger Alzheimer's disease years before symptoms appear -- can damage brain cells long before they become detectable by today's diagnostic methods.
Unlike the large amyloid plaques detected by current PET scans, these oligomers remain largely invisible using existing clinical tools. Their elusive nature has made them one of the greatest challenges in Alzheimer's research.
To overcome this obstacle, Prof. Rahimipour and colleagues in the Department of Chemistry at Bar-Ilan University developed a unique family of cyclic peptides that selectively bind to amyloid-beta oligomers while largely ignoring the larger plaques. Tagged with fluorescent molecules or radioactive copper, the compounds enable researchers to visualize these toxic aggregates in brain tissue and have the potential to become next-generation PET imaging agents for Alzheimer's disease.
In the newly published study, Dr. Michelle Ehrlich and Dr. Sam Gandy and colleagues at the Icahn School of Medicine at Mount Sinai used a specialized mouse model that accumulates soluble oligomers without forming conventional plaques. Rahimipour's molecular probes enabled the team to identify and characterize these elusive aggregates, demonstrating that they disrupt the mitochondria that power nerve cells and impair communication between neurons even before detectable inflammation develops.
"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."
The findings also have important implications for recently approved anti-amyloid therapies such as Lecanemab and Donanemab. Today, physicians primarily monitor treatment using biomarkers that reflect amyloid plaques, even though toxic oligomers may appear much earlier and may persist after treatment. Technologies capable of directly detecting oligomers could provide a more accurate picture of disease progression and treatment response.
Alzheimer's disease is believed to begin decades before symptoms emerge. Researchers believe that detecting oligomers during this silent phase could enable earlier intervention, improve patient selection for clinical trials, and provide more sensitive tools for evaluating new therapies.
Rahimipour's technology is now advancing toward clinical application. His team co-founded ApexBio, a startup developing the cyclic peptide platform for both diagnostic and therapeutic applications 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 targeting amyloid-beta oligomers as one of the most promising frontiers in Alzheimer's research.
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