Normal and AD patient–derived iPSCs, neural progenitor cells, and cortical neuronal cells were obtained from Axol Biosciences (Cambridge, UK). Control or disease iPS lines were generated using episomal vector reprogramming of somatic cells (newborn, male). In addition to control lines, in our study, we used iPSCs carrying mutation L286V in PSEN1 and mutation N141I in PSEN2, both of which are associated with EOAD. Age of patients when the skin cells were harvested for reprogramming was 38 years (female) and 81 years (female) for PSEN1 and PSEN2 lines, respectively. The iPSCs derived from a LOAD patient carrying homozygous APOE4 were generated by reprogramming fibroblasts harvested from a female patient at the age of 87 years. Directed differentiation of iPSCs to cortical neurons was performed as described previously (19). Characterization of iPSCs, neural progenitor cells, and cortical neurons in normal and AD patient–derived lines was performed at Axol Biosciences (Cambridge, UK). DNA samples originating from brain tissues of healthy (60 years, female), AD–frontal lobe region (87 years, male), and AD–left frontal lobe region (75 years, male) were purchased from BioChain (CA, USA). All samples were collected and processed according to protocols approved by the Brigham and Women’s Hospital.

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