Neuropathological immunohistochemistry of the E200G and a representative E200K case for comparison. (a-g E200G; h E200K) (a-b) insular cortex, (c) dentate nucleus, (d, i-j) putamen, (e, f) hippocampus, (g) thalamus, (h) E200K-129M thalamus. (a) Finely granular (synaptic) pattern of PrPSc accumulation occurs in layers V-VI, with a few larger PrPSc deposits (arrow). (b) H & E stain reveals vacuolation mostly in cortical layers V-VI. (c) A cerebellar dentate nucleus neuron shows granular deposits of PrPSc inside and around the perikarya and processes. (d) Many punctate linear and curvilinear arrays of PrPSc were located in the putamen. (e) Moderate to severe PrPSc accumulation is shown in the hippocampus, where (f) H & E stain shows no vacuolation (the same area as E). (g) H & E stain shows severe neuronal loss and reactive astrocytosis with mild vacuolation in the medial nucleus of thalamus (a representative astrocyte marked with an arrow). (h) H & E stain shows small vacuoles but neither neuronal loss nor reactive astrocytosis in the medial nucleus of thalamus of an E200K-129M patient (a representative neuron marked with an arrow). (i) PrPSc (red fluorescence) in the linear and curvilinear arrays contacts dendrites stained for MAP-2 (green fluorescence) along its course. (j) Some of PrPSc (red fluorescence) in the arrays is co-localized (yellow fluorescence, arrowheads) with synaptophysin (green fluorescence). Other PrPSc staining, however, is not co-localized, but in close proximity to synaptophysin., suggesting it is near pre-synaptic axonal terminals. Bars below b and c, 50 μm. Bar below d, 30 μm applying also to a. Bar below e, 100 μm, applying also to f. Bar below g, 50 μm applying also to h. Bar below i, 20 μm applying also to j. Layers of the cerebral cortex are indicated. “wm” indicates white matter.