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Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model
Published on: July 26, 2011
Molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl) amino]-2-naphthyl]ethylidene) malononitrile labels prion
Mara Bresjanac1, Lojze M Smid, Tomaz D Vovko
1Laboratory for Neuronal Plasticity and Regeneration, Institute of Pathophysiology, University of Ljubljana, SI-1000 Ljubljana, Slovenia. maja.bresjanac@mf.uni-lj.si
Abstract:
The study aimed to evaluate the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (FDDNP) for its ability to selectively and reproducibly label prion plaques in fixed, paraffin-embedded cerebellar sections from patients of confirmed Gerstmann-Sträussler-Scheinker disease, sporadic Creutzfeldt-Jacob disease (CJD) with kuru plaques, and variant CJD (vCJD). FDDNP is a highly hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent substance, whose radiofluorinated analog [18F]FDDNP has recently been successfully used to label senile plaques and neurofibrillary tangles in the living brain of Alzheimer's disease patients with positron emission tomography. Our results show that FDDNP reliably identifies all prion plaques, including small cluster-plaques in vCJD. This finding may open new in vivo diagnostic possibilities for vCJD.
Insights
The fluorescent probe FDDNP effectively labels prion plaques in brain tissue from various human prion diseases. This technique shows promise for future in vivo diagnostics of variant Creutzfeldt-Jakob disease (vCJD).
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Prion diseases, including Gerstmann-Sträussler-Scheinker disease, Creutzfeldt-Jakob disease (CJD), and variant CJD (vCJD), are fatal neurodegenerative disorders.
- Accurate diagnosis, especially for vCJD, remains challenging, necessitating improved diagnostic tools.
Purpose of the Study:
- To assess the efficacy of the fluorescent molecular-imaging probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene)malononitrile (FDDNP) in labeling prion plaques.
- To determine if FDDNP can selectively and reproducibly identify prion plaques in fixed, paraffin-embedded human cerebellar tissue.
Main Methods:
- Evaluation of FDDNP's fluorescent properties and its application to cerebellar sections from patients with confirmed prion diseases.
- Comparison of FDDNP labeling with histopathological findings of prion plaques, including kuru plaques and small cluster-plaques in vCJD.
Main Results:
- FDDNP reliably and reproducibly labeled all observed prion plaques across different forms of human prion disease.
- The probe successfully identified even small cluster-plaques characteristic of vCJD.
Conclusions:
- FDDNP is a sensitive and specific fluorescent probe for detecting prion plaques in fixed brain tissue.
- These findings suggest that FDDNP, or its radiofluorinated analog [18F]FDDNP, holds potential for in vivo diagnosis of vCJD and other prion diseases.

