No adaption of the prion strain in a heterozygous case of variant Creutzfeldt-Jakob disease

In 2016, the first definite case of clinical variant Creutzfeldt-Jakob disease (vCJD) in a 129MV individual was reported in the United Kingdom (1). The clinical features were consistent with either sporadic CJD (sCJD) or vCJD and brain magnetic resonance imaging (MRI) was suggestive of sCJD on diffusion weighted (DWI) sequences, although the single coronal FLAIR sequence in this case was not diagnostic because of movement artefact. CSF Real Time Quaking-induced Conversion assay analysis and Direct Detection Assay for vCJD infection in blood were negative. However at autopsy, neuropathological examination revealed florid plaques, and biochemical analysis of the brain PrP confirmed a Type 2B profile – both characteristic of vCJD (1). Abnormal PrP was also detected in peripheral tissues. Recent studies using Protein Misfolding Cyclic Amplification (PMCA) in CSF were positive in this case of vCJD, but not in sporadic cases, including those with a heterozygous genotype (2). Given the relatively atypical clinical features in the first confirmed case of vCJD in an 129MV individual, it is important to ascertain the strain of prion agent present to determine whether there has been strain adaption or whether the genetic background may have influenced the disease phenotype. We conducted a study to determine whether we could isolate the same prion strain from this case of vCJD in a 129MV individual as was identified in previous 129MM vCJD cases, consistent with the hypothesis of a causal link to BSE