Tau PET Imaging in Neurodegenerative Disorders

Area of Science:

• Neuroimaging
• Neuropathology
• Radiochemistry

Background:

• Positron emission tomography (PET) ligands targeting tau pathology enable in vivo quantification and visualization.
• Widely used tracers like 18F-flortaucipir bind to advanced Braak stage tau aggregates in Alzheimer's disease (AD).
• Quantification of non-AD tauopathies is challenging due to weaker tracer binding and significant off-target signals in regions like the substantia nigra and basal ganglia.

Purpose of the Study:

• To review the current state and limitations of tau PET tracers in clinical and research settings.
• To discuss the utility of tau PET in diagnosing and prognosing Alzheimer's disease and other tauopathies.
• To highlight methodological challenges and future directions for tau PET imaging.

Main Methods:

• Review of neuropathologic studies and clinical data on tau PET tracers (18F-flortaucipir, 18F-MK6240, 18F-RO948, 18F-PI2620).
• Analysis of tracer binding characteristics, including on-target and off-target binding patterns.
• Evaluation of tau PET performance in differentiating AD from non-AD conditions and its prognostic value.

Main Results:

• Tau PET tracers effectively quantify advanced AD tau pathology but show limited utility for non-AD tauopathies due to off-target binding.
• Neocortical tau PET signal in cognitively unimpaired individuals, even if amyloid-β positive, predicts cognitive decline.
• Tau PET demonstrates prognostic value in symptomatic AD, forecasting cognitive decline and brain atrophy.
• Tau PET is approved for differentiating AD dementia from other neurodegenerative diseases but has limited diagnostic performance at the mild cognitive impairment stage.

Conclusions:

• Tau PET is a valuable tool for diagnosing Alzheimer's disease dementia and holds prognostic potential.
• Methodological issues, particularly concerning off-target binding and reference region selection, are being addressed.
• Tau PET is transitioning towards clinical application for diagnosis, prognosis, and in clinical trials for participant selection and treatment monitoring.