Microglial PGRN protects against Aβ toxicity. (a–c) Spatial learning and memory in MWM in APPhigh mice. (a) Learning curve to locate the hidden platform. **, P < 0.01, by longitudinal mixed effects model with linear time trend. (b) Average swim speed across all training days. (c) Number of target platform crossings after 24 h (n = 11, n = 10, n = 9, n = 7, *, P < 0.05 by two-way ANOVA, Tukey-Kramer posthoc analyses). (d–g) Effects of viral PGRN overexpression in mixed cortical cultures. (d) Representative western blots of cell lysates from primary cultures infected with Lenti-MCSF-Ctrl or Lenti-MCSF-PGRN. Non-infected (NI). (e–g) Quantification of TUJ1 (e), GFAP (f), and Iba1 (g). n = 6 from three independent experiments performed in duplicates, **, P < 0.01 by one-way ANOVA, Tukey-Kramer posthoc analyses. (h–i) Effects of microglial PGRN on Aβ toxicity in vitro. (h) Representative western blot of supernatants from mixed cortical cultures infected with Lenti-MCSF-Ctrl or Lenti-MCSF-PGRN treated with Aβ oligomers (7PA2). (i) Aβ toxicity measured by survival of MAP2+ neurons. n = 84, n = 83, n = 82, n = 82 fields of view from two independent experiments, **, P < 0.01, ***, P < 0.001, by mixed effects model and multiple comparison correction using the method of Holm.