Following the establishment of positron emission tomography (PET) technology to visualize amyloid-β (Aβ) pathology, PET probes have been developed to capture pathological tau protein aggregates. Most clinically available probes exhibit the capability for facilitating the diagnosis of Alzheimer's disease (AD), while the detection of non-AD tau pathologies is offered by a few probes. The ultrastructure of disease-specific tau fibril folds has been revealed by cryo-electron microscopy, and the modes of the probe binding to these structures are being elucidated, potentially leading to progress in the generation of probes with high sensitivity and specificity. Tau PET holds promise for improving diagnostic accuracy, disease and subtype classifications, and staging of tauopathies. Similar to the clinical application of amyloid PET, tau PET is either approved or in clinical trials as a diagnostic tool. Additionally, tau PET is of significant utility for evaluating the impact of Aβ-targeting drugs on neuropathology and for selecting patients likely to benefit from treatment based on tau deposition levels. Furthermore, tau PET is expected to play a central role in clinical trials of therapeutics targeting tau pathologies by demonstrating mechanisms of action and providing objective outcomes.

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Advanced Tau Imaging in Alzheimer’s Disease and Other Types of Dementia

  • Kenji Tagai,
  • Makoto Higuchi

摘要

Following the establishment of positron emission tomography (PET) technology to visualize amyloid-β (Aβ) pathology, PET probes have been developed to capture pathological tau protein aggregates. Most clinically available probes exhibit the capability for facilitating the diagnosis of Alzheimer's disease (AD), while the detection of non-AD tau pathologies is offered by a few probes. The ultrastructure of disease-specific tau fibril folds has been revealed by cryo-electron microscopy, and the modes of the probe binding to these structures are being elucidated, potentially leading to progress in the generation of probes with high sensitivity and specificity. Tau PET holds promise for improving diagnostic accuracy, disease and subtype classifications, and staging of tauopathies. Similar to the clinical application of amyloid PET, tau PET is either approved or in clinical trials as a diagnostic tool. Additionally, tau PET is of significant utility for evaluating the impact of Aβ-targeting drugs on neuropathology and for selecting patients likely to benefit from treatment based on tau deposition levels. Furthermore, tau PET is expected to play a central role in clinical trials of therapeutics targeting tau pathologies by demonstrating mechanisms of action and providing objective outcomes.