In our 2-OPRI case series, three patients had immediate blood relatives with long-duration neurodegenerative disease presumed to be non-prion disease etiologies such as Alzheimer’s disease, but none of them underwent PRNP sequencing, and no autopsied brain material was examined to exclude prion pathology. The gene discussed is PRNP; the disease is early-onset autosomal dominant Alzheimer disease.