Fig. 1

The decrease in ACSS2 expression and histone acetylation in the cognition-related brain regions of middle-aged 5 × FAD mice and AD patients. A, B Representative immunoblots and western blot analysis of ACSS2 in the hippocampus (hippo.) and prefrontal cortex (PFC) of the 10-month-old wild-type (WT) and 5 × FAD mice (hippocampus, n = 5 per group; prefrontal cortex, n = 6 per group) (A). Representative images of sections through the dorsal hippocampus immunostained with ACSS2 (green), NeuN (red), and DAPI (blue) in the 10-month-old WT and 5 × FAD mice (B, left panel), with the quantification of ACSS2 intensity on CA1 NeuN + cells shown in the right panel (n = 3 mice for WT and n = 3 mice for 5 × FAD) (B, right panel). C Western blotting analysis of ACSS2 in the temporal cortex of AD patients and the healthy individuals (n = 5 per group). D Representative immunoblots and western blot analysis of ACSS2 in the cytosolic and nuclear fractions of the hippocampus from the 10-month-old WT and 5 × FAD mice (n = 8 mice for WT and n = 5 mice for 5 × FAD). E Relative acetyl-CoA levels in the whole-cell, nucleus, and cytoplasm of the hippocampus from the 10-month-old WT and 5 × FAD mice (n = 5-8 per group). F, G Immunoblots and western blot analysis of ac-H3K9/H3, ac-H3K27/H3, and ac-H4K12/H4 in the hippocampus (n = 5 per group) (F). Representative images of sections through the dorsal hippocampus immunostained with ac-H4K12 (green), NeuN (red), and DAPI (blue) in the 10-month-old WT and 5 × FAD mice (G, left panel), with the quantification of ac-H4K12 intensity on CA1 NeuN⁺ cells shown in the right panel (n = 3 mice for WT and n = 3 mice for 5 × FAD) (G, right panel). Data are expressed as mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001 by the unpaired two-tailed t-test