A similar organoid generation protocol98 employed in PSEN1 mutant A246E and PSEN2 mutant N141l recapitulated AD phenotypes such as aggregation of Aβ peptides, hyperphosphorylation of tau, increase in Aβ42/40 ratio, premature neuronal differentiation, and developmental and tissue pattern defects89. This evidence concerns the gene PSEN2 and Alzheimer disease.