Figure 2. Structural Equation Models (SEMs) Path Analyses Investigating the Association of Apolipoprotein E (APOE) ε4 on Transactive Response DNA-Binding Protein 43 (TDP-43).

A, These pathways were tested in the initial SEM and included all potential pathways. B, This SEM was the final model used. It became more parsimonious after eliminating pathways that were not significant at the P < .05 level. The arrowhead linking APOE ε4 to TDP-43 represents a direct association, and the arrowheads from APOE ε4 to Aβ to tau to TDP-43 represent indirect associations (mediation by Aβ and tau). Their sum represents the total association of APOE ε4 with TDP-43. The numbers on the arrowheads are estimated regression coefficients on the probit scale. The numbers leading into the same box can be compared, but the numbers leading into different boxes cannot because of differing measurement scales. Aβ indicates β-amyloid.

^aP < .05.

^bP < .01.

^cP <.001.