JAMA Neurol: KL-VSHET-Plus Genotype and Lower Risk of Alzheimer's Disease

Identifying genetic factors that interact with alleles of lipoprotein e4 (APOE4) can reduce the risk of Alzheimer's disease (AD) and accelerate the search for new AD drug targetsKlotho VS hybrids (KL-VSHET-state) prevent aging-related phenotypes and cognitive decline, but their effect on individuals carrying APOE4 is unclearRecently, researchers examined whether the status of KL-VSHET-plus in APOE4 carriers was associated with reduced AD risk and pathological changes in beta-amyloid protein (A-beta)study collected data from 25 individual case control, family-based and longitudinal AD cohort participants, stratified in APOE4 status, and genetic data was obtained from high-density single nucleotide variant microarraysThe main endpoint of the study was mild cognitive impairment (MCI) or AD riskof 36,530 participants, 13,782 were not eligible and not included in the end-of-term studyThe participants were 60 years of age and older, non-Hispanic, of Western Nordic descent, with cognitive normality and MCI or ADThe study found that the genotype KL-VSHET plus was associated with a reduced AD risk (0.75) in individuals 60 years of age or older with APOE4, which was more pronounced at age 60-80 (0.69 ratio)In addition, the risk of a KL-VS hybrid APOE4 carrier converting to MCI or AD is reduced (risk ratio 0.64)Finally, in the control group of APOE4 carriers aged 60-80, KL-VS hybridity was associated with lower A-beta in higher A-beta and PET scans in CSFstudy found that the risk of Alzheimer's disease in carriers of genotype KL-VSHET-plus was low, and that the study of the associated signaling pathways was expected to be a new target for the treatment of AD