PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease.
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.
Kepe
Vladimir
V
David Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-6948, USA.
Ghetti
Bernardino
B
Farlow
Martin R
MR
Bresjanac
Mara
M
Miller
Karen
K
Huang
Sung-Cheng
SC
Wong
Koon-Pong
KP
Murrell
Jill R
JR
Piccardo
Pedro
P
Epperson
Francine
F
Repovs
Grega
G
Smid
Lojze M
LM
Petric
Andrej
A
Siddarth
Prabha
P
Liu
Jie
J
Satyamurthy
Nagichettiar
N
Small
Gary W
GW
Barrio
Jorge R
JR
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
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