Browsing by Author "Smid, Lojze M."

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    PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease
    (Wiley, 2010-03) Kepe, Vladimir; Ghetti, Bernardino; Farlow, Martin R.; Bresjanac, Mara; Miller, Karen; Huang, Sung-Cheng; Wong, Koon-Pong; Murrell, Jill R.; Piccardo, Pedro; Epperson, Francine; Repovš, Grega; Smid, Lojze M.; Petrič, Andrej; Siddarth, Prabha; Liu, Jie; Satyamurthy, Nagichettiar; Small, Gary W.; Barrio, Jorge R.; Pathology and Laboratory Medicine, School of Medicine
    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.