Different types of plaques in a VV case of kuru.

Aims: Spread by ritual endocannibalism among the Fore linguistic group of Papua New Guinea, kuru was a uniformly fatal cerebellar ataxia syndrome. Here, we present a detailed study of amyloid plaques in archived brain from a well-documented kuru case, using electron microscopy, immunohistochemistry and confocal laser microscopy.

Material and Methods: We re-evaluated archival formalin-fixed, paraffin-embedded brain specimens, including cerebellum, cortical areas, hippocampus, and basal ganglia, of a 16-year-old male who died of kuru. Immunohistochemical stainings with antibodies against PrP, βAPP, pTau, alpha-synuclein, TDP43 and p62 were performed. Double and triple immunofluorescent stainings were used for confocal laser microscopy. 3D image analysis software with volume rendering was used to study the structure of the amyloid plaques.

Results: The immunohistochemistry  revealed diffuse PrP^Sc synaptic deposits in all areas examined. The typical unicentric kuru plaques were numerous in the granular layer of the cerebellar cortex but were also present in the striatum and hippocampal formation. Apart from these classic changes, we observed a few florid plaques similar to those described in vCJD and multi-centric plaques unique to GSS.  The multi-centric plaques, reconstructed into 3D-structural images, using confocal laser microscopy, showed several neurites crossing the amyloid plaques.

Conclusions:  We have identified three types of amyloid plaques in kuru: typical kuru plaques, multicentric plaques and florid plaques. Our study shows the similarity between the GSS plaques and kuru multicentric plaques in morphology and in the presence of tau-positive neurites.

The study was partly funded by National Science Centre project No 2023/05/Y/NZ2/00158