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

Abstract

ABSTRACTBACKGROUNDObesity is linked to a higher incidence of Alzheimer’s disease (AD). Studies show that plasma amyloid-β (Aβ) dyshomeostasis, particularly low 42/40 ratio indicates a heightened risk for developing AD. However, the relationship between body mass index (BMI) and circulating plasma Aβ has not been extensively studied.OBJECTIVEWe hypothesised that people with a high BMI have altered plasma Aβ homeostasis compared with people with a lower BMI. We also tested whether reducing BMI by calorie-restriction could normalise plasma concentrations of Aβ.METHODSPlasma concentrations of Aβ40, Aβ42and Aβ42/40ratio 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 Aβ concentrations.RESULTSPlasma Aβ42/40ratio 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 Aβ40(p=0.0425). However, weight loss showed negligible correlations with plasma Aβ40, Aβ42and Aβ42/40ratio.CONCLUSIONObesity is associated with aberrant plasma Aβ homeostasis which may be associated with an increased risk for AD. Weight loss appears to lower Aβ40, 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 Aβ homeostasis.