Fig. 4

Ablation of neurogenesis increases the expression of phosphorylated tau in the hippocampus of APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice. a Western blot of hippocampal protein extract from 4 month old APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice fed with vehicle or valganciclovir chow for 3 months (N = 3) shows that the expression level of full length amyloid precursor protein (APP) is comparable between the groups. However, there was a decrease in level of total tau and an increase in level of AT8-positive hyperphosphorylated tau (p-tau) in the valganciclovir-treated APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice. b-d Semi-quantitative analysis of Western blot using Image J normalized to actin. There was a trending increase in levels of (b) p-tau (AT8; two-tail, Welch’s unequal variance t-test, t _2.094  = 2.553, P = 0.1197), with no change in (c) total tau (Tau-5, two-tail, unpaired t-test, t ₄  = 0.9195, P = 0.4099) and (d) a significant increase in the ratio of p-tau to total tau (two-tailed, unpaired t-test; t ₄  = 4.368, P = 0.0120) in the brains of valganciclovir-treated APPswe/PS1ΔE9;Nestin-δ-HSV-TK. *P < 0.05. e Doublecortin (DCX) positive neuroblasts and immature neurons in the dentate gyrus of APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice fed with valganciclovir chow are immunoreactive for the anti-p-tau antibodies AT8. Immunoreactivity was not detected in APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice fed with vehicle. Scale bar = 10 μm. f Dot blot analysis of water soluble protein extract of the entorhinal cortex of APPswe/PS1ΔE9;Nestin-δ-HSV-TK mice fed with valganciclovir or normal chow reveals no difference in the level of A11 immunoreactive oligomeric Aβ between the groups (N = 3)