Figure 1.

Neurons derived from AD patients bearing a PSEN1 mutation exhibit reduced excitability. Whole cell patch clamping was performed on day 21–35 NGN2 iNs derived from fAD patients with a PSEN1^S290C (S290C) and PSEN1^A246E (A246E) and their respective CRISPR-corrected isogenic controls, S290^IC and A246^IC (A). (B) Representative current clamp recordings of membrane potential responses of all cell lines. The stimulation protocols consisted of one-second-long current injections from −100 pA to 140 pA in 10 pA steps. The colored traces indicate firing activity at rheobase. Neurons were tested for (C) resting membrane potential (RMP), (D) capacitance, (E) input resistance (Rin), (F) hyperpolarizing current induced membrane potential change (ΔMP), (G) rheobase, and (H) the number of action potentials fired at 2 times rheobase. Data is presented as the mean ± SEM. Each data point represents an individual cell (n = 7–41), from 3 independent differentiations. Data was analyzed using multiple t-tests with Holm-Sidak for multiple comparisons where *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. AD, Alzheimer’s disease; IC, isogenic control.