High leptin levels linked to lower risk of Alzheimer’s disease

A study has recently observed the possible protective effect of leptin against the development of Alzheimer’s disease (AD) by improving insulin sensitivity. 

Investigators conducted a comprehensive Mendelian randomization (MR) using genome-wide association studies to explore the causal effect of leptin and soluble leptin receptor (sLEPR) on AD and Parkinson’s disease (PD). They also performed multivariable MR to examine the role of BMI and insulin sensitivity index (ISI). 

Pooled estimates revealed the significant association of genetically proxied higher leptin levels with a reduced risk of AD (odds ratio [OR], 0.838, 95 percent confidence interval [CI], 0.741–0.948; p=0.005) but not PD. No significant associations were found between sLEPR levels and AD or PD. 

However, the protective effect of leptin on AD was attenuated to null following the adjustment of ISI (OR, 0.879, 95 percent CI, 0.758–1.018; p=0.086) but not BMI. AD and PD also showed no causal impact on circulating levels of leptin and sLEPR, which suggested the absence of reverse causation. 

Sensitivity analyses validated the strength of these associations, with no obvious pleiotropy and heterogeneity, according to the investigators. 

“Our findings underscore the distinct roles of leptin in AD and PD,” they said. 

Previous studies have shown a link between leptin, AD, and PD, but the causal relationship among them has not been established due to confounder and reverse causation, the investigators noted.