<i>ABCA1</i> rare variants interact with <i>APOE</i> isoforms to confer Alzheimer’s Disease risk

ABCA1 rare variants are associated with AD risk and the effect size appears to be modulated by APOE genotype, showing significant interaction with ε4 dosage. This suggests an interplay between ABCA1 and different ApoE isoforms in contributing to AD, highlighting a potential pathogenic mechanism. Further, as extracellular domain mutations show diverging impacts on AD risk depending on APOE genotype, this domain may play a critical role in the pathogenic interaction between ABCA1 and ApoE.