The advent of molecular imaging for in vivo visualization of amyloid and tau pathologies has revolutionized the field of Alzheimer disease (AD) research and offered valuable clinical and research tools to facilitate the early detection of AD-related pathology, increase diagnostic accuracy, and provide useful prognostic information regarding disease stage and future risk of cognitive decline in cognitively normal and impaired individuals. Several ligands that can reliably detect neuritic amyloid plaques, and one ligand that can detect neurofibrillary tangles constituted of hyperphosphorylated tau, have been FDA-approved for clinical use, while several other ligands are available for use in research settings. Amyloid positron emission tomography (PET) scans are useful in detecting early pathology in cognitively normal or impaired individuals, while tau PET scans provide information regarding disease stage and the spatial distribution of tau pathology, which corresponds to regional brain atrophy and impairment in specific cognitive domains. However, a few limitations should be considered when interpreting amyloid and tau PET scans. Amyloid PET scans may be abnormal in a significant portion of older adults, especially those who have one or more copies of the apolipoprotein E4 (APOE4) allele (referred to as APOE4 carriers) who may not progress to AD or experience symptoms during their lifetimes. Positive tau PET scans are most reliable in detecting advanced stages of tau pathology, typically seen in cognitively impaired individuals with mild to moderate dementia, and may be normal or show minimal changes in earlier disease stages. Amyloid and tau PET scans may assist in the differential diagnosis of AD, and tau PET scans may also assist in disease staging using the updated research criteria for AD. When interpreting amyloid and tau PET imaging, it is also important to consider differences in pharmacokinetics, binding affinities, and off-target binding across different tracers. In clinical settings, the interpretation of amyloid and tau PET scans relies mostly on visual assessments to determine whether a scan is “positive” or “negative”; however, several quantitative methods are available to estimate the regional burden of amyloid or tau pathology in research settings. We here describe the various ligands used in amyloid and tau PET imaging and summarize the current literature regarding their clinical, neuropathological and imaging correlates. We also review the published appropriate use criteria for amyloid PET imaging and discuss future directions in the use of amyloid and tau PET in the diagnosis or staging of AD.

Imaging Markers of Amyloid and Tau in Alzheimer Disease

章节
发表日期：

2025年

查看全文

Rawan Tarawneh

摘要

The advent of molecular imaging for in vivo visualization of amyloid and tau pathologies has revolutionized the field of Alzheimer disease (AD) research and offered valuable clinical and research tools to facilitate the early detection of AD-related pathology, increase diagnostic accuracy, and provide useful prognostic information regarding disease stage and future risk of cognitive decline in cognitively normal and impaired individuals. Several ligands that can reliably detect neuritic amyloid plaques, and one ligand that can detect neurofibrillary tangles constituted of hyperphosphorylated tau, have been FDA-approved for clinical use, while several other ligands are available for use in research settings. Amyloid positron emission tomography (PET) scans are useful in detecting early pathology in cognitively normal or impaired individuals, while tau PET scans provide information regarding disease stage and the spatial distribution of tau pathology, which corresponds to regional brain atrophy and impairment in specific cognitive domains. However, a few limitations should be considered when interpreting amyloid and tau PET scans. Amyloid PET scans may be abnormal in a significant portion of older adults, especially those who have one or more copies of the apolipoprotein E4 (APOE4) allele (referred to as APOE4 carriers) who may not progress to AD or experience symptoms during their lifetimes. Positive tau PET scans are most reliable in detecting advanced stages of tau pathology, typically seen in cognitively impaired individuals with mild to moderate dementia, and may be normal or show minimal changes in earlier disease stages. Amyloid and tau PET scans may assist in the differential diagnosis of AD, and tau PET scans may also assist in disease staging using the updated research criteria for AD. When interpreting amyloid and tau PET imaging, it is also important to consider differences in pharmacokinetics, binding affinities, and off-target binding across different tracers. In clinical settings, the interpretation of amyloid and tau PET scans relies mostly on visual assessments to determine whether a scan is “positive” or “negative”; however, several quantitative methods are available to estimate the regional burden of amyloid or tau pathology in research settings. We here describe the various ligands used in amyloid and tau PET imaging and summarize the current literature regarding their clinical, neuropathological and imaging correlates. We also review the published appropriate use criteria for amyloid PET imaging and discuss future directions in the use of amyloid and tau PET in the diagnosis or staging of AD.