Nonetheless, given that the APOE4 allele was recently found to induce LD accumulation, thereby impairing neuronal function29,30, our demonstration of the role of the LOAD risk allele at the PICALM locus in LD formation of iMG further strengthens the notion of a causal role of LD in mediating LOAD genetic risk factors, providing potential mechanistic targets for therapeutic development targeting AD. Here, APOE is linked to Alzheimer disease.