Box 2. Hypothetical model of seeded cerebral amyloid induction in mice.

An endogenous protein (panel a, blue) is not amyloidogenic under physiological conditions. In this case, the application of a seed (panel a, red) will not induce protein aggregation. A protein is amyloidogenic but does not aggregate during the lifespan of the mouse (which ends at the dotted line), either because endogenously formed seeds are removed by an effective proteostasis network, or because seed formation is inefficient and therefore unlikely to occur during the mouse’s lifetime (panel b, blue). However, with an appropriate seed (single inoculation), the onset of protein aggregation is advanced and occurs before the mouse reaches the end of its lifespan (panel b, red). A protein is highly amyloidogenic and typically aggregates with ageing of the mouse (panel c, blue). The addition of an appropriate seed advances the onset of protein aggregation (panel c, red).