CASP3 and Alzheimer disease: To examine if Aβ oligomers showed toxic effects to OSNs, we investigated the neurotoxicity induced by the Aβ1–42 peptide-derived diffusible ligands (ADDLs) in vitro using cultured OSNs.31 ADDLs induced OSN cell death with upregulated the cleavage of caspase-3, which is a final executor of apoptosis.32 In addition, phosphorylation of p38 MAPK, which is involved in the stress response33 (Figure 6e), was also increased, comparable to a previous report describing increased p38 MAPK activity in the AD human brain34 (Figure 6e).