APOE and Alzheimer disease: The frequency of the APOE ε4 allele is markedly increased to more than 40% in patients with AD, although the APOE ε4 allele has a worldwide frequency of 13.7%.[13] Our previous study reported that APOE ε4 carriers were 53.8% of 26 amyloid-positive CN, MCI and AD patients, who had a larger annual increase in Aβ deposition.[14] In the present study, in contrast, an APOE ε4 allele was present in 57.1% of amyloid-negative CN and MCI subjects who converted to amyloid-positive over time.