It is therefore possible to tag the haplotype associated with susceptibility to prion disease with a single nucleotide polymorphism (SNP), rs12249854 (A/T) that occurs within intron 1 of HECTD2. rs12249854 was genotyped in a panel of 320 samples from patients with a definite or probable diagnosis of AD and no known mutations in APP, PSEN1 or PSEN2. APOE genotypes were available for 316 individuals and showed enrichment for the ε4 allele (55.1% of individual have one or more ε4 allele). Here, PSEN1 is linked to prion disease.