Increased ubiquitination and phosphorylation of TDP-43 in the PGRN-deficient brain. (A) Enhanced ubiquitin immunostaining in the hippocampus of old PGRN-deficient mice. Sections from 18-mo-old WT and PGRN-deficient (KO) mice (n = 5) were stained using antibody against ubiquitin. Representative sections from two different mice in each group are shown. Bar, 80 µm. (B) Phosphorylation of TDP-43 and its cytosolic translocation in aged PGRN-deficient (KO) mice. Hippocampal and thalamic sections from 18-mo-old WT and PGRN-deficient mice (n = 5) were stained with antibodies against TDP-43 (top) or phosphorylated TDP-43 (bottom). Bars: (left and middle) 80 µm; (right) 12 µm.