Interdisciplinary dream team receives $3 million grant to revolutionize Alzheimer’s diagnosis

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What do a synthetic chemist, a medical imaging specialist, and a neurologist have in common? They are coming together at the Beckman Institute for Advanced Science and Technology’s Center for Biomedical Imaging to develop better diagnostic tools and imaging agents to detect early-stage Alzheimer’s disease and other neurodegenerative diseases.

dream team

A team led by Liviu M. Mirica Wawryzneic “Wawosz” Dobrucki and Dr. Daniel A. Llano received a $3 million grant from the US National Institute on Aging of the National Institutes of Health to develop and test multi-modal imaging agents for the detection of Alzheimer’s disease and related dementias. This grant is one of the first federal grants to bridge Beckman’s Magnetic Resonance Imaging Laboratory and Molecular Imaging Laboratory. They are both part of Beckman’s Center for Biomedical Imaging.

“I’m really excited about the opportunity to collaborate with different scientists in different fields.”

Liviu M. Mirica, synthetic chemist and William H. and Janet G. Lycan is Professor of Chemistry, School of Chemical Sciences, University of Illinois at Urbana-Champaign

His research group specializes in creating and characterizing synthetic inorganic molecules in vitro: outside the body.

Dobrucki, the Neil and Carol Ruzic Scholar for Biomedical and Translational Sciences, is an imaging specialist who works extensively with PET scanning in Beckman’s Molecular Imaging Laboratory.

“I look forward to high-resolution imaging of the brain and its structures,” Dobrucki said.

Llano, a professor of molecular and integrative physiology and a physician-surgeon, is a practicing neurologist who sees patients every day and specializes in the study of the in vivo brain: the one inside the body.

“What I’m most excited about is the potential impact this project will have on Alzheimer’s,” Llano said.

Understanding Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative disease that negatively affects brain function and cognitive abilities. Alzheimer’s falls into the category of amyloid disease, along with Parkinson’s disease, amyotrophic lateral sclerosis, and other disorders. Amyloid is a small group of abnormal fibers or misfolded proteins that normally serve no purpose in the body.

A key marker of Alzheimer’s disease is the presence of amyloid plaques: large clumps of small beta-amyloid peptide aggregates. Peptides are short chains of amino acids that eventually make up proteins. Neuroinflammation and oxidative stress in the brain are also key markers of Alzheimer’s.

Diagnosing and treating neurodegenerative diseases is particularly difficult because the blood-brain barrier, a semipermeable system of blood vessels and capillaries that regulates the flow of ions, molecules and cells between the blood and the brain. To be effective, imaging agents and drug therapy (made with molecules or antibodies) must pass.

Diagnosis and treatment

Diagnosis of Alzheimer’s disease with a high degree of accuracy requires detection of amyloid aggregates and can only be completed during postmortem investigation. This creates a need for diagnostic tools that can rapidly detect soluble beta-amyloid peptide aggregates and larger amyloid plaques in the living patient.

PET and MRI are two non-invasive imaging methods commonly used in clinical settings. However, no MRI contrast agents that target amyloid aggregates have been developed. Some FDA-approved PET imaging agents are insufficient to detect small-scale amyloid abnormalities or, in some cases, lead to false-positive test results when diagnosing Alzheimer’s.

Developing diagnostic tools to target small beta-amyloid peptides and other signs of neuroinflammation and oxidative stress is important for several reasons, Mirica said. Developing a multi-modal tool that can be used for both PET and MRI scans will give researchers a better idea of ​​who is at risk of developing Alzheimer’s, who actually has the disease, and at what stage.

$3M plan

Mirica, Dobrucki, and Llano will receive a $3 million grant over 5 years to develop novel dual-purpose imaging agents that can easily cross the blood-brain barrier and are compatible with both PET and MRI scanners.

This will enable the detection of neurodegenerative diseases at an early stage and “greatly help the development of better therapies,” Mirica said.

Brad Sutton, a professor of bioengineering and technical director of Beckman’s Center for Biomedical Imaging, will assist the team by performing in vivo MRI studies. They will then evaluate the imaging agent’s ability as a dual modality diagnostic agent for Alzheimer’s disease and related dementias.

Meanwhile, Mirica and his colleagues have developed a series of customized molecules that can cross the blood-brain barrier and help detect both the small soluble beta-amyloid peptide and the larger insoluble amyloid.

They also developed a copper-based PET imaging agent that led to successful imaging of amyloid plaques in transgenic Alzheimer mice. Looking ahead, the team believes these agents can be developed to cross the blood-brain barrier in humans and image multiple markers of Alzheimer’s disease and other neurodegenerative diseases at an early stage.

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