Fig. 2
Neuronal deletion of NCLX accelerates AD pathology. a Schematic of NCLX knockout 3xTg-AD mutant mouse gene-targeting strategy. b NCLX mRNA expression, corrected to the housekeeping gene, Rps13; expressed as fold change vs. Camk2a-Cre control, n = 4 for all groups. c Western blots for NCLX expression in tissue isolated from the hippocampus of mice. VDAC and CV-Sα, served as mitochondrial loading controls. d, e Y-maze spontaneous alternation test. d Percentage of spontaneous alternation. e Total number of arm entries. f–h Fear-conditioning test. f Freezing responses in the training phase. g Contextual recall freezing responses, h Cued recall freezing responses. i, j Soluble and insoluble Aβ1–40 and Aβ1–42 levels in cortex of 12-month-old mice. k Representative immunohistochemical staining for 4G8-reactive β-amyloid; 4× scale bar = 100 μm, 40× scale bar = 50 μm. l Quantification of the integrated optical density area for Aβ immunoreactivity, n = 4 for all groups. m Western blots of full-length APP, ADAM-10, BACE1, PS1, Nicastrin, APH, and tubulin (loading control) for cortex homogenate of 12-month-old mice. n Representative western blots of soluble and insoluble total tau (HT7), phosphorylated tau at residues S202/T205 (AT8), T231/S235 (AT180), T181 (AT270), and S396 (PHF13) in cortex homogenate of 12-month-old mice, n = 3 for all groups. o Representative immunohistochemical staining for total tau (HT7) and phospho-tau S202/T205 (AT8) in hippocampus of mice; scale bar = 50 μm. p, q Quantification of the integrated optical density area of HT7 and AT8 immunoreactivity, n = 4 for all groups. (n = individual dots shown for each group in all graphs. All data presented as mean ± SEM; ****p < 0.001, **p < 0.01, *p < 0.05; one-way ANOVA with Sidak's multiple comparisons test.) Source data are available as a Source Data file
