SEQUENTIAL APPEARANCE AND ACCUMULATION OF PATHOGNOMONIC MARKERS IN THE CENTRAL-NERVOUS-SYSTEM OF HAMSTERS ORALLY INFECTED WITH SCRAPIE

Both infectivity and TSE-specific amyloid protein (also referred to as protease resistant- or prion protein, PrP) are pathognomonic markers for transmissible spongiform encephalopathies (TSE). This paper presen ts a new densitometric method for the quantification of TSE-specific a myloid protein and its application to studying the pathogenesis of scr apie in Syrian hamsters after infection with scrapie strain 263K. A fi rst study established a close correlation between infectivity and TSE- specific amyloid protein with a doubling time of 2-2 . 6 days in the b rain and cervical spinal cord for both markers. The ratio of infectivi ty and TSE-specific amyloid protein was relatively constant at a mean value of about 10(6) protein molecules per infectious unit during the course of infection. A subsequent study addressed the temporal-spatial spread of infection in the central nervous system by tracing the accu mulation of the pathological protein. The pathogenetic process was fi rst detected in the spinal cord between vertebrae T4 and T9, and then showed an anterograde and retrograde spread with a rate of 0 . 8-1 . 0 mm/day. There were also some indications for a possible alternative r oute of spread of infection from the periphery to the brain, other tha n via the spinal cord. Involvement of the spleen did not appear essent ial for the early pathogenesis in hamsters orally infected with the 26 3K strain of scrapie.