Cortical circuit principles predict patterns of trauma induced tauopathy in humans.

In brains of individuals who had sustained repetitive head trauma, advanced pathologic tau protein in neurons and axons within temporal cortices followed patterns seen in homologous cortico-cortical connections in nonhuman primates. The relational Structural Model, which is based on the universal principle of the systematic variation of cortical laminar structure, has successfully predicted the relative laminar distribution of cortico-cortical connections based on the relative similarity/difference in laminar structure in pairs of linked areas. Here, the Structural Model successfully predicted the graded laminar distribution and density of pathologic tau in chronic traumatic encephalopathy and was validated by a computational progression model. By contrast, early and sporadic tau pathology in the depths of sulci in chronic traumatic encephalopathy followed local columnar connectivity rules. These findings support applicability of a theoretical model to unravel the direction and progression of tau pathology in neurodegeneration via cortical connection mechanisms. Cortical pathways converging on temporal cortices may help explain the inexorable spread of pathologic tau to widespread cortical areas accompanied by decline in emotional and cognitive processes in humans with repetitive head trauma.