Evidence from spatial pattern analysis for the anatomical spread of α-synuclein pathology in Parkinson's disease dementia

The objective of this study was to determine whether there is evidence from quantitative morphometry and spatial pattern analysis to support the hypothesis of anatomical spread of α-synuclein in Parkinson's disease dementia (PDD). Hence, clustering of α-synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) was studied in α-synuclein-immunolabeled sections of cortical and limbic regions in 12 cases of PDD. The data suggested that: (1) LB, LN, and LG occurred in clusters which in 63% of regions were regularly distributed parallel to the tissue boundary, (2) in approximately 30% of cortical regions, the estimated cluster size of LB, LN, and LG was within the size range of cellular columns associated with the cortico-cortical pathways, (3) regularly distributed clusters were present in anatomically connected regions, and (4) the clustering pattern was similar to that of prion protein (PrPsc) deposits in Creutzfeldt-Jacob disease (CJD). The clustering patterns of LB, LN, and LG were similar to those exhibited by cellular inclusions in other synucleinopathies and by PrPsc deposits in prion disease and therefore, anatomical spread of pathogenic α-synuclein could be involved in the pathogenesis of PDD