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Figure S1. Astrocytic and microglial activation. (a) Stratum lacunosum-moleculare (SL) showing moderate astrocytosis and mild vacuolation. Bar = 200 μm. Immunohistochemistry for GFAP. (b) Stratum lacunosum-moleculare showing mild microglial activation and mild vacuolation. Bar = 100 μm. Immunohistochemistry for coronin. (c) Severe astrocytosis in the superior colliculus associated with marked vacuolation. Bar = 200 μm. Immunohistochemistry for GFAP. (d) Severe microgliosis associated with marked vacuolation in the midbrain tectum. Bar = 100 μm. Immunohistochemistry for coronin. (e) Marked astrocytosis is present around several sub-ependymal plaques (arrowheads). Bar = 100 μm. Immunohistochemistry for GFAP. (f) Small numbers of activated microglia are present in the neuropil adjacent to amyloid plaques (arrowheads) in the periventricular glial limitans. Bar = 100 μm. Immunohistochemistry for coronin.

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Figure S2. Tau immunolabelling: cerebral cortex showing moderate vacuolation and punctuate tau immunolabelled structures. Bar = 50 μm. Immunohistochemistry for tau.

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Figure S3. Area postrema. (a) A large areas of neuropil surrounding a blood vessel shows loss of normal architecture, increased extracellular space and a dystrophic neurite (d). Bar = 3 μm. Uranyl acetate/lead citrate. (b) Detail of an area similar to the above, showing loss of normal cellular processes and replacement by poorly defined fibrillar (arrowheads) PrPSSLOW amyloid fibrils. Bar = 0.5 μm. Immunogold for PrPSSLOW. (c) Accumulation of PrPSSLOW in association with convoluted and microfolded processes, and poorly defined fibrils (arrowheads) surrounding a large astrocytic process (A). Bar = 1 μm. Immunogold for PrPSSLOW.

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Figure S4. Enlarged mitochondria: enlarged mitochondria with abnormal christae were mostly located in glial cell cytoplasm. A normal mitochondrion is present at M. Bar = −0.5 μm. Uranyl acetate/lead citrate.

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