It has been hypothesized by O'Grady et al. that the ε4 allele of APOE may predispose individuals to ARHL by the same mechanisms as for Alzheimer's disease (via predisposition to auditory neuropathy) or atherosclerotic vascular disease (via ischemic injury to the cochlea).18 In contrast to this theory, the authors found that APOE ε4 was at a lower frequency in a study population with sensorineural hearing loss (89 subjects, median age 64, 38 females) compared to the general population, suggesting a protective influence. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.