Given the association of TMCC2 with both APP and apoE, and the established roles of these two proteins in AD pathogenesis, we investigated TMCC2 distribution in 19 AD cases having different genetic susceptibilities, either five cases each of APOE3 or APOE4 homozygotes in late onset AD as well as in five age‐matched controls, together with early onset AD associated with Down syndrome (three cases) or familial AD associated with APP mutated at Val717 (six cases). Here, TMCC2 is linked to Down syndrome.