Assessing the Benefit of Dietary Choline Supplementation Throughout Adulthood in the Ts65Dn Mouse Model of Down Syndrome.

Background/objectives: Down syndrome (DS) is the most common cause of early-onset Alzheimer's disease (AD). Dietary choline has been proposed as a modifiable factor to improve the cognitive and pathological outcomes of AD and DS, especially as many do not reach adequate daily intake levels of choline. While lower circulating choline levels correlate with worse pathological measures in AD patients, choline status and intake in DS is widely understudied. Perinatal choline supplementation (Ch+) in the Ts65Dn mouse model of DS protects offspring against AD-relevant pathology and improves cognition. Further, dietary Ch+ in adult AD models also ameliorates pathology and improves cognition. However, dietary Ch+ in adult Ts65Dn mice has not yet been explored; thus, this study aimed to supply Ch+ throughout adulthood to determine the effects on cognition and DS co-morbidities.

Methods: We fed trisomic Ts65Dn mice and disomic littermate controls either a choline normal (ChN; 1.1 g/kg) or a Ch+ (5 g/kg) diet from 4.5 to 14 months of age.

Results: We found that Ch+ in adulthood failed to improve genotype-specific deficits in spatial learning. However, in both genotypes of female mice, Ch+ significantly improved cognitive flexibility in a reverse place preference task in the IntelliCage behavioral phenotyping system. Further, Ch+ significantly reduced weight gain and peripheral inflammation in female mice of both genotypes, and significantly improved glucose metabolism in male mice of both genotypes.

Conclusions: Our findings suggest that adulthood choline supplementation benefits behavioral and biological factors important for general well-being in DS and related to AD risk.