As expected, the levels of P-tau at Ser396, as one of the important pathological features and biomarkers of AD [31], were significantly upregulated in the shSirt1 group compared to the control group (t2 = 6.020, p = 0.004) and the sham group (t2 = 6.400, p = 0.003) (Fig. 4D). Here, MAPT is linked to Alzheimer disease.