Imaging tau pathology in Parkinsonisms

Area of Science:

• Neuroimaging
• Neurology
• Radiochemistry

Background:

• Positron emission tomography (PET) radiotracers targeting pathological tau are crucial for in vivo diagnosis.
• Research has predominantly focused on Alzheimer's disease, neglecting other tauopathies like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
• Tau aggregates exhibit diverse isoforms and conformations, necessitating specific radiotracers for accurate detection in different parkinsonian tauopathies.

Purpose of the Study:

• To review and evaluate preclinical and clinical data of current tau PET radiotracers in parkinsonian tauopathies.
• To assess the suitability of various radiotracers for detecting tau pathology in conditions beyond Alzheimer's disease.
• To identify potential limitations and concerns associated with existing tau PET tracers in these disorders.

Main Methods:

• Review of preclinical and clinical studies on tau PET radiotracers.
• Analysis of radiotracer binding in patients with progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia and parkinsonism linked to chromosome 17.
• Evaluation of radiotracer specificity and potential off-target binding.

Main Results:

• Radiotracers evaluated include [18F]FDDNP, [11C]PBB3, [18F]THK-5317, [18F]THK-5351, and [18F]AV-1451 ([18F]T807).
• [18F]FDDNP and [11C]PBB3 show concerns regarding off-target binding, potentially reducing efficacy.
• [18F]THK-5317 and [18F]THK-5351 demonstrated binding in affected brain regions in PSP and CBD, but require replication due to small sample sizes.
• [18F]AV-1451 yielded mixed results in PSP and showed minimal binding to non-Alzheimer's tauopathies in post-mortem analyses.

Conclusions:

• Current tau PET radiotracers show variable efficacy in parkinsonian tauopathies.
• [18F]THK-5317 and [18F]THK-5351 show potential but need larger studies for validation.
• [18F]AV-1451 appears less suitable for non-Alzheimer's tauopathies.
• Further research is essential to develop and validate specific radiotracers for diverse parkinsonian tauopathies.