As expected, 7–10 month-old Grn–/– mice exhibited lipofuscinosis throughout the forebrain (A–D, RM ANOVA effect of genotype, p = 0.0022, n = 5–7 mice per group). In contrast, neither LysM-Cre+, CaMKII-Cre+, nor LysM-Cre+:CaMKII-Cre+ mice exhibited lipofuscinosis relative to Cre– littermates (B–D, RM ANOVA effect of CaMKII-Cre, p = 0.831, effect of LysM-Cre, p = 0.513, CaMKII-Cre x LysM-Cre interaction, p = 0.549, n = 5–10 mice per group) at 22–24 months of age. Grn–/– mice also exhibited elevated SCMAS (E–H, RM ANOVA effect of genotype, p < 0.0001, n = 5–6 mice per group), a protein component of lipofuscin, while LysM-Cre+, CaMKII-Cre+, and LysM-Cre+:CaMKII-Cre+ mice did not (E–H, RM ANOVA effect of CaMKII-Cre, p = 0.093, effect of LysM-Cre, p = 0.184, CaMKII-Cre x LysM-Cre interaction, p = 0.414, n = 4–10 mice per group). Scale bars represent 50 µm. VPM/VPL = ventroposteromedial/ventroposterolateral thalamus. ** = p < 0.01, *** = p < 0.001, and **** = p < 0.0001 by t test.