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In this issue

Infection in scrapie occurs via the oral route, but the routes of neuroinvasion are unclear. Early involvement of the dorsal motor nucleus of the vagus nerve in the brain stem and of the intermediolateral cell column of the thoracic cord have suggested that the disease-associated prion protein may spread to the central nervous system (CNS) via the enteric/autonomic nervous system. However, there is also early circulating infectivity, raising the question of a role for a haematogenous route. Siso et al. have hypothesized that if direct autonomic nervous system spread is responsible for the targeting of the specific brain regions affected, the topographic distribution will differ if other routes of infection are used. However, using a number of different routes, they show similar topographic patterns of CNS infection with consistent early involvement of dorsal motor nucleus of the vagus nerve and hypothalamus. Their results support a haematogenous route as an alternative or parallel pathway of neuroinvasion. They also show early involvement of circumventricular organs, brain structures lacking the blood brain barrier, suggesting that these may act as the portal of entry.