ABSTRACT
BACKGROUND Obesity 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.
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 reducing BMI by calorie-restriction could normalise plasma concentrations of Aβ.
METHODS Plasma concentrations of Aβ40, Aβ42 and Aβ42/40 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 Aβ concentrations.
RESULTS Plasma Aβ42/40 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 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 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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
This version of the manuscript has been revised to update grammar, flow, and clarity. Such changes were made through the entire document.
