Humans with Alzheimer’s disease (AD) exhibit progressive cognitive impairment, neurodegeneration, formation of amyloid beta (Aβ) plaques, and neurofibrillary tangles - features that have not been fully recapitulated in animal models (Elder et al., 2010). Linkage studies have uncovered mutations in certain genes causing autosomal dominant forms of AD (ADAD), including presenilin (PSEN1, PSEN2), amyloid precursor protein (APP), and a moderately penetrant polymorphism, APOE-e4 (for AD genetics overview, see (Bagyinszky et al., 2014)). APOE isoforms have differential effects on disease progression: whereas APOE2 is protective and APOE3 is neutral, APOE4 appears to constitute a major risk factor for AD (Strittmatter et al., 1993). Investigation of APOE isoforms in iPSC-derived human neurons has provided novel insights into molecular pathways of neural APOE, such as the differential efficacy of APOE isoforms in activating an unusual MAPK cascade regulating APP gene regulation (Huang et al., 2017). Another study ascribes a neurotoxic function for APOE4 that can be ameliorated with a small-molecular structure corrector, predicting a novel and potentially protective AD therapy (Wang et al., 2018). An innovative single-cell analytical platform for detecting secreted Aβ
