In a recent study, the combined effect of the APOε4 allele and KLOTHO variants in a large longitudinal AD cohort was explored, and the protective effect of KLOTHO variants (KL-VS) was powerfully demonstrated against the APOε4 allele by reducing the risk of converting healthy patients carrying the APOε4 allele from aging to mild cognitive impairment (MCI). This evidence concerns the gene KL and Alzheimer disease.