Figure 9.

Tau_RD/ΔK280 reduces spine-synapse density and synaptic markers. A, Stratum radiatum of CA1 region of hippocampus. Coronal brain sections from control, proaggregation, and antiaggregation mice were immunostained for the presynaptic marker synaptophysin. Immunohistochemistry staining was performed on animals after 9 months of Tau_RD gene expression and age-matched nontransgenic littermates. B, Quantification of staining shows that synaptophysin is strongly decreased in proaggregation mice [e.g., by ∼70% in the CA1 region (n = 9–16; mean ± SE; p < 0.001) and by ∼56% in the CA3 region (n = 9–16; mean ± SE; * p < 0.05)]. C, Quantification of spinophilin immunostaining in the CA1 and CA3 region shows no significant differences between proaggregation and antiaggregation mice, and a slight decrease compared with nontransgenic littermates (n = 9–16; mean ± SE). D, E, Brain sections from proaggregation and antiaggregation (9.5 months ON) mice were imaged by electron microscopy (stratum radiatum of the CA1 region). F, Quantitative evaluation of spine-synapses in the stratum radiatum of the CA1 hippocampal region. Note the decrease by 27% of the spine synapse number in the proaggregation mutant compared with antiaggregation and control mice (proaggregation mice had 6.7 ± 0.7 spine-synapses per 6.4 μm³; antiaggregation mice had 9.7 ± 0.5 spine synapses per 6.4 μm³; wild-type mice had 9.2 ± 0.6 spine synapses per 6.4 μm³) (n = 10; mean ± SE; *** p < 0.001). Scale bars: A, 40 μm; D, E, 600 nm.