TSE Transmission to Sea Bream Figure 4. Abnormal deposits in the brains of the BSE- and the scrapie-challenged fish with reference to time. Each dot corresponds to the number of aggregates observed per brain section in each individual before PK-treatment (A, D) and after PK digestion (B, E), or to the percentage of PK-resistant aggregates in each BSE-challenged fish (C). Bars indicate the means and the standard error means (SEMs). doi:10.1371/journal.pone.0006175.g004 neurites that have lost their coherence, with spicule-like projec- tions, at their periphery (Fig. 8A, D, G, J). Given that aggregates were partially PK-resistant and showed affinity for Congo red by 24 months, the next step in the progression may have been the complete deconstruction of the fibers leading to the creation of a homogenous, flocculated, extracellular material that we describe as ‘‘mature’’ deposits (Fig. 8B, E, H, K), with increased PrP- immunopositivity, PK-resistance, congophilia and birefringence in polarized light [35]. Fish brains at 24 months post inoculation exhibit both types of abnormal aggregates, including intermediate PLoS ONE | www.plosone.org 6 July 2009 | Volume 4 | Issue 7 | e6175