The ease with which large numbers of these organoids can be created, and their ability to respond to compound treatment, open the possibility for phenotypic and mechanistic compound screening in complex human tissue models of multiple neurodegenerative diseases. With iPSC technology, we can access patient-derived cells carrying AD-associated variants in a number of genes, which are difficult to model as many are non-coding and/or associated with more than one significant single-nucleotide polymorphism (SNP) [75]. Moreover, rapid improvements in gene editing technology allows researchers to create isogenic iPSC and ESC lines that carry disease-associated coding variants, both well-known (such as in the APOE gene, [76,77] or emerging (i.e. SORL1 [50,78], TREM2, [79]). Together, these advancements allow us to conceive of systems in which we can test candidate therapies on complex neural tissue systems targeted to defined subpopulations of late-onset or sporadic AD patients.
