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Yonsei University Professors Uncover True Identity of Alzheimer's PET Tracer 18F-THK5351

From Hankyoreh · () Korean

Translated from Korean, summarized and contextualized by DistantNews.

At a glance

News Official statement Context piece
  • Researchers have identified that a PET tracer used for Alzheimer's disease, 18F-THK5351, primarily binds to the MAO-B enzyme in reactive astrocytes, which drive neuroinflammation, rather than the previously assumed Tau protein.
  • This discovery, achieved through multimodal validation including computer simulations and clinical imaging, clarifies the tracer's mechanism and offers a standard model for developing and verifying PET tracers for neurodegenerative diseases.
  • The findings, published in Experimental & Molecular Medicine, are crucial for early diagnosis and the development of treatments for Alzheimer's disease by accurately tracking MAO-B in the living brain.

A joint research team from Yonsei University and the Institute for Basic Science (IBS) has revealed the true identity of a PET tracer, 18F-THK5351, commonly used in Alzheimer's disease research. Previously believed to target Tau protein, the tracer actually binds predominantly to MAO-B, an enzyme found in reactive astrocytes that are key drivers of neuroinflammation.

Alzheimer's disease, the most common cause of dementia, is increasingly understood to involve reactive astrocytes accelerating disease progression in its early stages. The enzyme MAO-B within these cells is known to induce neurodegeneration and cell death, making it a critical biomarker for early diagnosis and treatment development. However, accurately tracking MAO-B in the living brain using PET imaging has been hampered by an unclear understanding of existing tracers' targets and mechanisms.

The research team employed a rigorous "multimodal validation" approach. This involved a comprehensive pipeline that spanned molecular enzyme inhibition analysis, computer simulations, human brain tissue examination, genetically modified animal models, and clinical PET imaging from actual patients. This systematic cross-validation confirmed that the 18F-THK5351 signal reflects MAO-B-mediated reactive astrocytes, not just Tau pathology.

This breakthrough clarifies that the 18F-THK5351 imaging signal mirrors the 'MAO-B mediated reactive astrocytes' crucial for Alzheimer's progression. The study, published in the journal Experimental & Molecular Medicine, is expected to set a standard model for the development and validation of PET tracers for neurodegenerative diseases. The findings are significant for advancing early diagnosis and therapeutic strategies by providing a more precise tool to track disease mechanisms in the brain.

18F-THK5351 primarily binds to the 'MAO-B' enzyme, which drives neuroinflammation in brain reactive astrocytes, rather than the Tau protein as previously known.

— Yonsei UniversityDescribing the core finding of the research.
DistantNews Editorial

Originally published by Hankyoreh in Korean. Translated, summarized, and contextualized by our editorial team with added local perspective. Read our editorial standards.

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