These can be made in vitro by applying heat or chemical denaturants to wild type or mutant variants of neuroserpin [45], and are formed in vivo as a consequence of point mutations that destabilise neuroserpin, leading to a rare neurodegenerative dementia called FENIB (familial encephalopathy with neuroserpin inclusion bodies, discussed in detail below). The gene discussed is SERPINI1; the disease is familial encephalopathy with neuroserpin inclusion bodies.