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

Vladimir Kepe, Bernardino Ghetti, Martin Farlow, Mara Bresjanac, Karen Miller, Sung Cheng Huang, Koon Pong Wong, Jill R. Murrell, Pedro Piccardo, Francine Epperson, Grega Repovš, Lojze M. Smid, Andrej Petrič, Prabha Siddarth, Jie Liu, Nagichettiar Satyamurthy, Gary W. Small, Jorge R. Barrio

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)419-430
Number of pages12
JournalBrain Pathology
Volume20
Issue number2
DOIs
StatePublished - Mar 2010

Fingerprint

Amyloid
Brain
Neocortex
Thalamus
Cerebellum
Glucose
Caudate Nucleus
Prions
Brain Diseases
Rare Diseases
2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile
Prion Proteins
Basal Ganglia
Neurodegenerative Diseases
Genes
Disease Progression
Magnetic Resonance Imaging
Pathology
Mutation

Keywords

  • [F-18]FDDNP
  • [F-18]FDG
  • Amyloid
  • Familial prion disease
  • GSS A117V
  • GSS F198S "Indiana kindred"
  • GSS P102L
  • Positron emission tomography
  • PRNP gene mutation
  • Tau
  • Transmissible spongiform encephalopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease. / Kepe, Vladimir; Ghetti, Bernardino; Farlow, Martin; 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.

In: Brain Pathology, Vol. 20, No. 2, 03.2010, p. 419-430.

Research output: Contribution to journalArticle

Kepe, V, Ghetti, B, Farlow, M, Bresjanac, M, Miller, K, Huang, SC, Wong, KP, Murrell, JR, Piccardo, P, Epperson, F, Repovš, G, Smid, LM, Petrič, A, Siddarth, P, Liu, J, Satyamurthy, N, Small, GW & Barrio, JR 2010, 'PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease', Brain Pathology, vol. 20, no. 2, pp. 419-430. https://doi.org/10.1111/j.1750-3639.2009.00306.x
Kepe, Vladimir ; Ghetti, Bernardino ; Farlow, Martin ; 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. / PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease. In: Brain Pathology. 2010 ; Vol. 20, No. 2. pp. 419-430.
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