Doable new PET tracer for early detection of Alzheimer’s

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Possible new PET tracer for early detection of Alzheimer's

Astrocytes in the brain of a deceased patient with Alzheimer's disease. (Right) The black arrows show astrocytes surrounding amyloid plaques in the brain of a deceased patient with Alzheimer's disease. Photo credit: Amit Kumar.

New biomarkers for Alzheimer's disease are a priority area for researchers who want to learn more about the disease and find possible ways to detect it early. Researchers at the Karolinska Institutet in Sweden have now examined a new PET tracer that is an important diagnostic tool for the disease. The study on the tracer substance BU99008, published in Molecular Psychiatry, may play a key role in the early detection of signs of Alzheimer's disease.

According to Alzheimer Disease International (ADI), Alzheimer's disease is the most common form of dementia, affecting nearly 47 million people worldwide. This number is expected to increase as life expectancy increases.

The disease is not yet incurable and causes considerable suffering for both patients and their families.

Alzheimer's is an insidious disease in which changes in brain function set in 10 to 20 years before clinical cognitive decline. It is therefore important to identify early disease markers.

One such marker is reactive astrogliosis, which reacts early and quickly to the progression of the disease. Astrocytes are the most important homeostatic cells in the central nervous system (CNS) with a wide range of functions for optimal brain function and cellular energy supply, homeostasis.

They are also implicated in disease and CNS damage through the defense process called reactive astrogliosis.

The pathological role astrocytes play in Alzheimer's disease is not fully understood, but several studies suggest that reactive astrogliosis may precede known early pathological signs of Alzheimer's disease, including amyloid plaque and tau tangles.

Possible new PET tracer for early detection of Alzheimer's
The binding of the BU99008 PET tracer reveals reactive astrogliosis in different parts of the brain of a deceased patient with Alzheimer's disease. The colors indicate the extent of the bond, with green being low, yellow being medium, and red being high. Photo credit: Amit Kumar

Researchers therefore need to develop tracers for the astrocyte response for use in PET scans. PET imaging diagnostic technology uses selective and specific tracers – radioactive chemical molecules – for the early detection of pathological conditions and is already routine in detecting abnormal neuronal functions and amyloid loads in the brain, such as those caused by Alzheimer's disease.

Researchers at the Karolinska Institutet, Uppsala University, and Indiana University School of Medicine in the United States have investigated a new astrocytic PET tracer, BU99008, that appears to show promise for Alzheimer's disease.

The researchers used brain tissue from six people who had died from Alzheimer's and seven healthy controls who had died from other causes. The results provide a better understanding of BU99008 binding properties compared to other brain biomarkers for Alzheimer's disease in astrocytes.

"Our study shows that BU99008 can detect key reactive astrocytes with good selectivity and specificity, making it a potentially important astrocyte PET clinical tracer," says first author of the paper, Amit Kumar, a researcher in the Department of Neurobiology, Nursing Sciences and society, Karolinska Institutet. "The results can improve our understanding of the role of reactive astrogliosis in Alzheimer's disease."

"As far as we can tell, this is the first time that BU99008 has made reactive astrogliosis visible in the Alzheimer's disease brain," says lead researcher Agneta Nordberg, a professor in the same department. "The results can have far-reaching clinical implications that cover other disorders of reactive astroglial dysfunction."

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More information:
Amit Kumar et al. The astroglia tracer BU99008 visualizes astrogliosis and detects multiple binding sites in the brain of Alzheimer's disease, Molecular Psychiatry (2021). DOI: 10.1038 / s41380-021-01101-5

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Karolinska Institutet

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