KL and Cognitive impairment: 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).