Fig. 1: REST and the onset of AD pathology.
From: A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer’s disease
a Induction of REST in neurons with early AD pathology. Labeling of REST (green), the early tau pathology marker pSer202-tau (antibody CP13, red) and DNA (DAPI, blue) in the aging human prefrontal cortex shows increased nuclear REST in an NCI case with early AD-type pathology relative to no pathology, and reduced REST levels in AD. CP13 labeling (red) shows broad accumulation of phosphorylated tau in neurites, and in some neuronal cell somas, in NCI cases with early pathology (middle panel), and a strong increase in tau accumulation in neurites and neuronal cell bodies in AD (lower panel). Scale bar, 25 µm. b Quantification of nuclear REST levels in pyramidal neurons of the prefrontal cortex in NCI cases with no pathology (n = 21), early pathology (n = 30), mid pathology (n = 26) and late pathology (n = 5), as well as in AD cases with no pathology (n = 3), early pathology (n = 3), mid pathology (n = 13) and late pathology (n = 44). Neurons were identified by co-labeling with the neuron marker MAP2 (see Supplementary Fig. 1d). See Supplementary Fig. 1b for the relative distribution of each level of pathology in NCI and AD cases. P-values were generated by two-way ANOVA with Tukey’s post-hoc test. The interaction between cognitive status and pathology stage was significant: F(3, 136) = 3.68, P = 0.013). c Reduced nuclear REST in AD. The mean nuclear REST level is significantly reduced in AD (n = 63) relative to NCI cases (n = 82). Individual values and the mean ± S.E.M are shown. P < 10−12 by two-tailed unpaired t-test. Source data are provided as a Source Data file.
