Histopathologically, while most prion diseases, including CJD, BSE, CWD, and most of scrapie cases (i.e., the classic transmissible spongiform encephalopathies or TSEs), are characterized by the triad of spongiform change, gliosis, and neuronal loss, some rare but very informative variants such as FI, GSS, or PrP-CAA may show very subtle or even absent spongiform change or be characterized by prominent extracellular amyloid plaques accumulating either in the neuropil or around blood vessels. This evidence concerns the gene PRNP and scrapie.