title: PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease.
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.
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-6948, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.forename: Mara
authors.initials: M
authors.lastname: Bresjanac
authors.forename: Karen
authors.initials: K
authors.lastname: Miller
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Koon-Pong
authors.initials: KP
authors.lastname: Wong
authors.forename: Jill R
authors.initials: JR
authors.lastname: Murrell
authors.forename: Pedro
authors.initials: P
authors.lastname: Piccardo
authors.forename: Francine
authors.initials: F
authors.lastname: Epperson
authors.forename: Grega
authors.initials: G
authors.lastname: Repovs
authors.forename: Lojze M
authors.initials: LM
authors.lastname: Smid
authors.forename: Andrej
authors.initials: A
authors.lastname: Petric
authors.forename: Prabha
authors.initials: P
authors.lastname: Siddarth
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D016098:Gerstmann-Straussler-Scheinker Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009570:Nitriles; D049268:Positron-Emission Tomography; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D000682:Amyloid; C054369:MAPT protein, human; D009570:Nitriles; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D016875:tau Proteins; D019788:Fluorodeoxyglucose F18; D005947:Glucose