Adult choline supplementation in a Down syndrome model reduces co-morbidities and improves cognition

Abstract

Down syndrome (DS) is the most common cause of early-onset Alzheimers disease (AD). Dietary choline has been proposed as a modifiable factor to improve cognitive and pathological outcomes of AD, especially as many do not reach adequate daily intake levels. Perinatal choline supplementation (Ch+) in the Ts65Dn mouse model of DS protects offspring against AD-relevant pathology and improves cognition, and dietary Ch+ in adult AD models also ameliorates pathology and improves cognition. However, dietary Ch+ in adult Ts65Dn mice has not yet been explored. To test whether Ch+ in adulthood improves DS co-morbidities, we fed trisomic Ts65Dn mice and disomic littermate controls with either choline normal (ChN; 1.1 g/kg) or Ch+ (5 g/kg) diets from 4.5-14 months of age. We found that Ch+ improved cognitive flexibility in a reverse place preference task and reduced weight gain and peripheral inflammation in female mice, whereas Ch+ improved glucose metabolism in male mice. In conclusion, we found that adulthood Ch+ benefits behavioral and biological factors important for general well-being in DS and related to AD risk.