[F-18]FDDNP PET imaging of prion pathology in Gerstmann-Sträusller-Scheinker disease

Abstract

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Objectives: Gerstmann-Sträusller-Scheinker disease (GSS) is a genetic prion disease linked to the PRNP gene mutations resulting in prion proteins more prone to misfolding and pathological aggregation via β-pleated sheet formation. [F-18]FDDNP PET imaging was used for in vivo visualization of prion pathology in the brains of 5 carriers of GSS related PRNP gene mutations, and compared with 5 age matched controls and 5 Alzheimer’s disease (AD) patients. Methods: [F-18]FDDNP and [F-18]FDG positron emission tomography (PET) was performed in 2 symptomatic GSS patients with F198S mutation, one GSS patient with P102L mutation, 2 asymptomatic subjects with F198S mutation, and in 5 age matched control subjects and 5 AD patients. Two GSS subjects returned for the follow-up [F-18]FDDNP scans after one year. Quantitative analysis of [F-18]FDDNP data was performed using Logan graphical analysis with white matter as reference region. Relative distribution volume (DVR) maps were generated, spatially normalized to MNI space and the subjects compared using a set of ROIs. Results: GSS patients had elevated [F-18]FDDNP binding in cerebellum, thalamus and striatum, when compared with controls and ADs. The cortex was affected showing [F-18]FDDNP binding patterns different from AD, in which [F-18]FDDNP binds to beta-amyloid and tau aggregates. Of two asymptomatic F198S mutation carriers one had [F-18]FDDNP binding elevated only in striatum and thalamus and the other was indistinguishable from controls. [F-18]FDG uptake in 3 GSS patients was decreased in all affected areas, most notably in striatum and/or thalamus. At the one year follow-up no changes were detected for one asymptomatic subject, spreading of [F-18]FDDNP cortical binding pattern was observed in the P102L GSS patient. Conclusions: This study demonstrates feasibility of in vivo PET detection of prion pathology with [F-18]FDDNP, and possibility of monitoring of the disease progression. At least in F198S GSS subjects, prion deposition may appear first in subcortical structures later extending to cerebellum and cortex, which may explain their progressive motor and behavioral symptoms.