PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease.

TitlePET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease.
Publication TypeJournal Article
Year of Publication2010
AuthorsKepe, V, Ghetti B, Farlow MR, Bresjanac M, Miller K, Huang S-C, Wong K-P, Murrell JR, Piccardo P, Epperson F, Repovs G, Smid LM, Petric A, Siddarth P, Liu J, Satyamurthy N, Small GW, Barrio JR
JournalBrain pathology (Zurich, Switzerland)
Volume20
Issue2
Pagination419-30
Date Published2010 Mar
ISSN1750-3639
KeywordsAdult, Aged, Alzheimer Disease, Amyloid, Brain, Female, Fluorodeoxyglucose F18, Follow-Up Studies, Gerstmann-Straussler-Scheinker Disease, Glucose, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Nitriles, Positron-Emission Tomography, Prions, tau Proteins
Abstract

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.

Alternate JournalBrain Pathol.