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

Abstract

BACKGROUNDObesity is linked to a higher incidence of Alzheimers disease (AD). Studies show that plasma amyloid-{beta} (A{beta}) dyshomeostasis, particularly low 42/40 ratio indicates a heightened risk for developing AD. However, the relationship between body mass index (BMI) and circulating plasma A{beta} has not been extensively studied. OBJECTIVEWe hypothesised that people with a high BMI have altered plasma A{beta} homeostasis compared with people with a lower BMI. We also tested whether reducing BMI by calorie-restriction could normalise plasma concentrations of A{beta}. METHODSPlasma concentrations of A{beta}40, A{beta}42 and A{beta}42/40 ratio were measured in 106 participants with BMIs classified as lean, overweight, or obese. From this cohort, twelve participants with overweight or obese BMIs entered a 12-week calorie-restriction weight loss program. We then tested whether decreasing BMI affected plasma A{beta} concentrations. RESULTSPlasma A{beta}42/40 ratio was 17.54% lower in participants with an obese BMI compared to lean participants (p<0.0001), and 11.76% lower compared to participants with an overweight BMI (p<0.0001). The weight loss regimen decreased BMI by an average of 4.02% (p=0.0005) and was associated with a 6.5% decrease in plasma A{beta}40 (p=0.0425). However, weight loss showed negligible correlations with plasma A{beta}40, A{beta}42 and A{beta}42/40 ratio. CONCLUSIONObesity is associated with aberrant plasma A{beta} homeostasis which may be associated with an increased risk for AD. Weight loss appears to lower A{beta}40, but large-scale longitudinal studies in addition to molecular studies are required to elucidate the underlying mechanisms of how obesity and weight loss influence plasma A{beta} homeostasis.