C9orf72 and amyotrophic lateral sclerosis: Moreover, the presence of known pathogenic mutations associated with FTLD-TDP (such as C9orf72 and GRN) are incompatible with a diagnosis of LATE-NC, and an earlier age of onset, high burden of middle frontal gyrus TDP-43 immunoreactive inclusions, and TDP-43 inclusions in subcortical structures, the brainstem, or spinal cord should favor a diagnosis of FTLD-TDP and/or ALS.