neural supplement, and 1% (v/v) Penicillin/Streptomycin/Amphotericin b solution without growth factors. A half volume of the differentiation media was changed every 3 days for 3–7 weeks. DAPT, Compound E and BACE inhibitor IV were purchased from EMD Millipore, N-Lauroylsarcosine (Sarkosyl) from Sigma-Aldrich. Hematoxylin QS from Vector Laboratories (Burlingame, CA, USA), and Amylo-Glo from Biosensis (Thebarton, Australia). SGSM41 is an aminothiazole-bridged heterocycle-containing soluble γ-secretase modulator (SGSM) similar in structure to those published recently19. SGSM 41 has the typical characteristics of this series of SGSM molecules that potently inhibit the production of Aβ42 and to a lesser degree Aβ40 while concomitantly increasing the generation of shorter Aβ peptide species such as Aβ38 and Aβ37. The structures and the detailed properties are included in Extended Data Table 1.