PRNP expression predicts imaging findings in sporadic Creutzfeldt-Jakob disease

Objective: We explored the relationship between regional PRNP expression from healthy brain tissue and patterns of increased and decreased diffusion and regional brain atrophy in patients with sporadic Creutzfeldt-Jakob disease (sCJD). Methods: We used PRNP microarray data from 6 healthy adult brains from Allen Brain Institute and T1-weighted and diffusion-weighted MRIs from 34 patients diagnosed with sCJD and 30 age- and sex-matched healthy controls to construct partial correlation matrices across brain regions for specific measures of interest: PRNP expression, mean diffusivity, volume, cortical thickness, and local gyrification index, a measure of cortical folding. Results: Regional patterns of PRNP expression in the healthy brain correlated with regional patterns of diffusion signal abnormalities and atrophy in sCJD. Among different measures of cortical morphology, regional patterns of local gyrification index in sCJD most strongly correlated with regional patterns of PRNP expression. At the vertex-wise level, different molecular subtypes of sCJD showed distinct regional correlations in local gyrification index across the cortex. Local gyrification index correlation patterns most closely matched patterns of PRNP expression in sCJD subtypes known to have greatest pathologic involvement of the cerebral cortex. Interpretation:These results suggest that the specific genetic and molecular environment in which the prion protein is expressed confer variable vulnerability to misfolding across different brain regions that is reflected in patterns of imaging findings in sCJD. Further work in larger samples will be needed to determine whether these regional imaging patterns can serve as reliable markers of distinct disease subtypes to improve diagnosis and treatment targeting.

Automated summary

This study investigated the relationship between regional PRNP expression in healthy brain tissue and diffusion abnormalities and atrophy patterns in patients with sporadic Creutzfeldt-Jakob disease (sCJD). PRNP microarray data from healthy brains and T1-weighted and diffusion-weighted MRIs from sCJD patients and healthy controls were used to examine correlations between PRNP expression, diffusion measures, cortical morphology, and local gyrification index. The results showed that regional patterns of PRNP expression were associated with diffusion abnormalities and atrophy in sCJD, with the local gyrification index exhibiting the strongest correlation. These findings suggest that the genetic and molecular environment influence the vulnerability of different brain regions to misfolding of the prion protein, which is reflected in imaging findings in sCJD. Larger studies are needed to validate these regional imaging patterns as reliable markers for distinct disease subtypes.