On 13 April, Dr Michael Belloy and colleagues published a paper in JAMA Neurology, reporting a lower risk of developing Alzheimer’s disease (AD) inApoE4carriers heterozygous for the VS variant of theKlothogene.
ApoE4 is one of the strongest and most prevalent genetic risk factors for AD, associated with increased amyloid beta deposition in the brain and earlier onset of disease. Genetic risk factors such as ApoE4 are thought to interact with each other, as well as with other factors such as age, lifestyle and health status – leading to alterations in the AD risk profile. Two recent, small-scale studies identified a potential interaction between the Klothogene and ApoE4. However, the studies revealed opposing results, with the Klotho VS variant (denoted as KL-VS) conferring some or no protection against amyloid accumulation. The KL-VS genotype is thought to be relatively common, with an estimated prevalence of 20%.
To evaluate the interaction between Klotho and ApoE4 with greater confidence, Dr Belloy and colleagues analysed the publicly-available, anonymized data from 25 independent case-control, family-based and longitudinal AD cohorts, including the ADNI (Alzheimer’s Disease Neuroimaging Initiative) and ROSMAP (Religious Orders Study and Memory and Ageing Project) cohorts. In total, analyses of datasets from 24,743 participants were performed, evaluating (among other criteria) ApoE4 status, Klothogenotype, age, amyloid beta burden and conversion to AD. Their analyses revealed that ApoE4 carriers who also carried the KL-VS variant were at reduced risk of developing AD, particularly between the ages of 60 and 80 (odds ratio of 0.69). Moreover, in cognitively normal ApoE4 carriers, possession of the KL-VS genotype was associated with lower amyloid beta deposition in the brain, as measured by PET scans. The original article was published in JAMA Neurology and can be found here:
https://jamanetwork.com/journals/jamaneurology/fullarticle/2763599?resultClick=1
