Deposition of the prion protein (PrP) during the evolution of experimentalCreutzfeldt-Jakob disease

We studied the immunocytochemical distribution of the prion or proteinase-r esistant protein (PrP) during the evolution of experimental Creutzfeldt-Jak ob disease (CJD) in mice. Fifty-one brains were collected up to 22 weeks fo llowing intracerebral inoculation with the Fujisaki strain of the CJD agent . Slides were also immunostained for apolipoprotein E (apoE) and glial fibr illary acidic protein. Vacuolar changes with focal astrocytosis first occur red around the needle track at week 2 and later spread along white matter t racks. Until week 12, changes were asymmetrical, affecting more the side of inoculation. Spongiform change and astrogliosis spread subsequently to the gray matter. Time course and intensity of spongiform change and immunocyto chemistry for PrP were discrepant: in most brain regions, severe vacuolatio n preceded immunocytochemically detectable PrP accumulation. PrP deposits i n form of small dots were first detectable at week 6 in the area surroundin g the needle track. After week 7, plaque-like amorphous PrP deposits were o bserved in white matter pathways. Finally, PrP was detectable also in basal ganglia and in the dorsal hippocampus (week 13) and in the neocortex (week 17), as the synaptic type of PrP immunopositivity. In the hippocampus, dif fuse PrP deposits paralleled spongiform change, while in the cortex severe vacuolation was accompanied only by weak synaptic PrP deposits. Immunocytoc hemically detectable apoE was restricted to compact plaque-type PrP deposit s after week 15. We conclude that disease-specific neuropathology spreads f rom the needle track along white matter pathways towards the gray matter; i n this model, there is some discrepancy between development of tissue patho logy and immunocytochemically detectable deposition of PrP. Immunocytochemi cally detectable apoE deposition follows PrP accumulation.