hTDP-43 protein expression was induced via intracerebroventricular injection of AAV9.CAG.hTDP-43 in neonatal mouse (AAV9.CAG.Empty as control). a, Schematic representation of the velocity sedimentation protocol for separating soluble from Sarkosyl-insoluble aggregated proteins from an aqueous homogenate of brain tissue. b, Whole brain hTDP-43 and p-hTDP-43 (Ser409/410) immunoblots of the soluble fraction of WT and TREM2 KO mice at 70 dpi. p-hTDP-43 (Ser409/410) antibody detected a ~25 kD fragment in the soluble fractions. Notably, Ser409/410 is at the extreme C-terminal of TDP-43 protein, suggesting a higher level of phosphorylated C-terminal fragments in TREM2 KO mice. c, Whole brain p-hTDP-43 immunoblots of the Sarkosyl-insoluble fraction of WT and TREM2 KO mice at 70 dpi. Western blots were independently repeated twice with n = 4 for each group.