Single-cell sequencing of cerebral organoids with familial Alzheimer’s disease (AD) mutation in PSEN1 and non-demented control

We set up a 3D model based on iPSCs derived from patients with familial forms of Alzheimer’s disease (AD) and healthy non-demented control. We created cerebral organoids (COs), verified their ability to mimic AD in vitro, and used it to explore early events and the progression of AD pathogenesis. Our data reveal that despite similar expression of cell-type-specific genes during CO maturation in vitro, AD-iPSCs derived COs show limited tissue patterning and altered cellular development. These findings complement unique single-cell sequencing data of AD-iPSCs derived COs confirming this observation and uncovering that a sub-set of neurons in AD-iPSCs likely differentiates prematurely while at the same time retaining the expression of progenitor marker PAX6.