Submicroscopic immunodetection of PrP in the brain of a patient with a new-variant of Creutzfeldt-Jakob disease.

We analyzed the distribution and organization of the pathological prion protein isoform (PrPsc) in the brain of new variant Creutzfeldt-Jakob disease using a sensitive post-embedding immunogold electron microscopy method. On methacrylate semithin sections, silver-PrP staining showed florid plaques, containing microvacuoles. It also revealed scattered granular and perivacuolar deposits. At the electron microscope level, plaque PrP-gold labeling was associated with filaments and flocculent amorphous material sometimes observed inside microvacuoles, considered as degenerative neurites. Outside the plaques, PrP-gold labeling was predominantly found over flocculent amorphous material and the presynaptic domain of synapses. Some lysosome-like organelles seen in the neuron perikaryon, were also found to be PrP-immunoreactive. These results are consistent with the hypothesis that the synapse is a privileged target in prion disease.