Our results show that TDP-43 pathology in the ATPC, but not in the OFC, represents an early neocortical stage in the progression of TDP-43 pathology in aging and AD being intermediate between stage 2 (mesial temporal) and the later stages with more widespread neocortical TDP-43 distribution and that involvement of the ATPC is an important pathologic marker of the transition to dementia. The gene discussed is TARDBP; the disease is dementia.