Fig. 3: MAPT−/− iPSC-derived cortical neurons demonstrate reductions in neuronal activity and protection from Aβ-driven hyperactivity.

A Representative raster plots showing individual neuronal activity spikes for each of the sixteen electrodes (row) in each MEA well over 2 min for both Day 90 MAPT+/+ and MAPT−/− neurons (MAPT−/− #1 from the Exon 1 panel) from each isogenic panel at baseline; Quantification of baseline neuronal activity parameters measured by MEA assays on Day 90–100 iPSC-derived cortical neurons from both MAPT−/− isogenic panels. Mean ± SEM. n = 53–55 (Exon 1 MAPT+/+) or 51–53 (Exon 1 MAPT−/−) wells across three independent neuronal differentiation repeats; 101–105 (Exon 4 MAPT+/+) or 103–114 (Exon 4 MAPT−/−) wells across six independent neuronal differentiation repeats. Some wells did not achieve the threshold needed to register network activities. Two-tailed Mann-Whitney test was used for statistical analysis. B Representative raster plots showing individual neuronal activity spikes for each of the sixteen electrodes (row) in each MEA well over 2 min for both Day 90 Exon 4 MAPT+/+ and MAPT−/− neurons treated with either AD brain homogenate or Aβ-immunodepleted (ID) AD brain homogenate at 25% v/v in the neuronal media for 5 days; Quantification of neuronal activity parameters measured by MEA assays over 5 days on Day 90–93 Exon 4 MAPT+/+ and MAPT−/− iPSC-derived cortical neurons treated with either AD brain homogenate or Aβ-ID homogenate at 25% v/v in the neuronal media. All datapoints were normalised to the baseline recording pre-treatment, and for each time point relative to the wells subject to aCSF (vehicle) control treatment. Mean ± SEM. n = 7–14 (MAPT+/+ID), 11–14 (MAPT+/+AD) or 5–16 (MAPT−/− ID and AD) wells across three independent neuronal differentiation repeats. Two-way ANOVA with Dunnett’s multiple comparison correction was used for statistical analysis compared against the MAPT+/+AD wells 5 days post-treatment.