Objective: The objective of our study is to investigate the  use of THK-5351 tau- PET-imaging as an additional tool for differential diagnosis in hypokinetic-rigid syndromes suggestive for Parkinson’s disease and atypical Parkinsonian syndromes.

Background: The pathophysiology of neurodegenerative typical or atypical parkinsonian syndromes is characterized by deposition of fibrillar aggregates either of tau protein or alpha-synuclein in neuronal and/or glial cells in affected brain areas. Increasing efforts are taken to develop interventions against defined molecular target structures to develop a disease modifying therapy targeting either alpha-synuclein or tau aggregate pathology. As these distinct molecular pathologies can manifest clinically as overlapping syndromes, it is becoming increasingly important to establish biomarkers yielding an ante mortem diagnosis of the underlying pathology. The clinical diagnosis of PSP, a primary tauopathy, is based on clinical criteria and MRI findings, which do not take tau pathology into consideration. The presence of tau- deposits is a key finding leading to the neuropathological diagnosis of „definite PSP“, which is usually established post mortem.

Therefore, we aim to investigate the utility of THK-5351-PET as a tool to diagnose the presence of tau pathology in hypokinetic-rigid syndromes in vivo.

Methods: Patients with possible or probable PSP or MSA-P according to current criteria received THK-5351 PET scanning. PET scans were co-registered to MRI. A visual as well as a semi-quantitative analysis of tracer binding (standardized uptake value ratio) in predefined brain areas was performed using the cerebellar cortex as reference region. Disease severity measured by the PSP Rating Scale, Unified Multiple System Atrophy Rating Scale, Schwab and England Activities of Daily Living scale and disease duration were assessed.

Results: Increased THK-5351 binding was detectable in striatum, thalamus and brainstem, especially in the midbrain in patients with PSP compared to patients with MSA or healthy controls.

Conclusions: THK-5351 binding patterns correlated well with the known distribution of tau-pathology at autopsy in PSP. Higher THK-5351 retention was evident in patients with PSP compared to patients with MSA and healthy controls. THK-5351 seems to be a useful biomarker of tau deposition and may therefore facilitate differential diagnosis of hypokinetic-rigid syndromes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/utility-of-thk-5351-tau-pet-for-differential-diagnosis-in-patients-with-hypokinetic-rigid-syndromes/