This is consistent with colon being the only tissue besides CNS and PNS to be affected in prion disease: patients with C-terminal truncating mutations that remove PrP’s GPI anchor and cause a gain of function through change in localization often experience chronic diarrhea misdiagnosed as inflammatory bowel disease for decades before the onset of peripheral neuropathy and then dementia30,31. This evidence concerns the gene PRNP and prion disease.