Electron microsocopy of brain amyloid plaques from a patient with new variant Creutzfeldt-Jakob disease.

Cerebral cortex biopsy from a patient with new variant Creutzfeldt-Jakob disease (nvCJD) has been examined at the electron microscope level. Spongiform changes corresponded mostly to distended neurites scattered in the neuropil or surrounding amyloid plaques. These latter exhibited heterogeneous submicroscopic morphology including variable amount of loosely interwoven amyloid fibrils admixed in a cellular-rich environment constituted essentially by abnormal neuronal processes. By immunoelectron microscopy, fibrils and some membrane structures reacted with anti-prion protein (PrP) antibodies. One striking aspect was the presence of many small dystrophic neurites without paired helical filaments. Moreover, amyloid fibrils showed unexpected intimate association with abnormal membranes, suggesting a relationship between PrP fibrillogenesis and membrane alteration. These ultrastructural findings provide an additional criterion to distinguish nvCJD-from sporadic CJD-type plaques and reinforce the hypothesis that nvCJD brain is infected by a distinctive strain of the transmissible agent encephalopathy.