Plasma amyloid-beta homeostasis is associated with Body Mass Index and weight-loss in people with overweight and obesity

BACKGROUND Obesity is linked to a higher incidence of Alzheimer’s disease (AD). Studies show that plasma amyloid-β (Aβ) dyshomeostasis, particularly 42/40 ratio indicates heightened risk of developing AD. However, the relationship between body mass index (BMI) and circulating plasma Aβ have not been extensively studied. OBJECTIVE We hypothesised that people with a high BMI have altered plasma Aβ homeostasis compared with people with a lower BMI. We also tested whether lowering BMI by calorie-restriction normalises plasma concentrations of Aβ. METHODS The plasma concentrations of Aβ40, Aβ42 and Aβ42/40 ratio were measured in 106 participants who were classified as either lean, overweight, and obese, based on their BMI. 12 overweight/obese participants from the cohort of 106 individuals, were thereafter subjected to a 12-week calorie-restriction weight-loss program. We then tested whether the decreased BMI shows any correlation with plasma Aβ levels. RESULTS Obese participants showed significantly lower mean plasma Aβ42/40 ratio compared to lean (17.54%, p<0.0001) and overweight participants (11.76%, p<0.0001). The weight-loss regimen decreased BMI by an average of 4.148%, and was associated with a 6.5% decrease in plasma Aβ40 (p=0.0425). However, weight loss showed negligible correlations with plasma Aβ40, Aβ42 and Aβ42/40 ratio. CONCLUSION Obesity is associated with aberrant plasma Aβ homeostasis which may be associated with an increased risk for AD. Weight-loss shows some influence of Aβ, but further studies are required to elucidate the underlying mechanisms of how obesity induces plasma Aβ dyshomeostasis and the complete effect of weight-loss on Aβ metabolism.