Fig. 4

Early-stage tau and Aβ disrupt hippocampal somatostatin interneurons, while parvalbumin cells are spared until 15 months. We assessed the accumulation of tau pathology within hippocampal interneurons of 9-, 12- and 15-month-old TgF344-AD rats, by co-localization of PHF1 with GABAergic subtypes: PVB and SST (representative images from n = 6–12 sections/group). a No co-localization was detected between PHF1 and PVB at 9 and 12 months of age. At 15 months, hippocampal PVB neurons exhibited cytoplasmic tau accumulation (white arrows). b Conversely, hippocampal SST interneurons exhibited cytoplasmic (white arrows), and less commonly dendritic PHF1 staining at as early as 9 months of age. c Quantification of SST⁺/PHF1⁺ co-localization at 9, 12 and 15 months of age, and PVB⁺/PHF1⁺ co-localization at 15 months in Tg rats showed significant increases in SST-tau pathology over age, and more affected cells than PVB-tau at 15 months. d Compared to NTg, the 15-month-old Tg rats had a visually degenerative hippocampal SST network with stunted processes, and cell bodies that clustered around Aβ plaques (yellow arrowheads). e The percentage of dystrophic SST neurons (quantified as plaque-associated) significantly increases with age in Tg rats. f Quantification of dendritic length from SST neuronal traces showed overall significant genotype differences in CA1 (P = 0.02). g In the DG, Tg rats exhibited a significant loss in SST dendritic length at all 3 ages. Scale bars, 20 μm (a, b) and 100 μm (c). Data are mean ± SEM (c, e: n = 3 rats/age, 6 hippocampi/rat; f, g: from n = 16 cells/cohort, sampled across 4 rats/genotype at each age); one-way (c and e) and two-way (f and g) ANOVA with correction for multiple comparisons with a Holm-Sidak post hoc test; *P < 0.05; ***P < 0.001