Model of the possible pathways of aerogenic prion transmission.

(left) Prion aerosols entering the nasal cavity (1) may directly migrate through the nasal epithelium towards olfactory nerve terminals (2). Subsequently, prions reach olfactory bulb neurons and colonize the limbic system and other regions of the brain (3). Prions may be taken up by the eyes from where they could be transported via the visual system (e.g. optic nerves) to the CNS. O: olfactory system; V: visual system. Alternatively (right) prions may be taken up by immune cells residing in (1) the nasal cavity, the lung, or (2) the gastrointestinal tract, from where they may be transferred to lymphoreticular system (LRS) components such as bronchial lymph nodes (BALT), nasal associated lymphoid tissue (NALT), gastrointestinal lymphoid tissue (GALT), mesenteric lymph nodes, or spleen for further amplification. Subsequently, prions traffic towards peripheral nerve terminals (PNS), from where they invade the central nervous system (CNS). SC: spinal cord. Arrows indicate possible migration directions of prions once they have invaded the spinal cord.