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

Tallino, S.; Etebari, R.; McDonough, I.; Leon, H.; Sepulveda, I.; Winslow, W.; Bartholomew, S. K.; Perez, S.; Mufson, E. J.; Velazquez, R.

doi:10.1101/2024.09.26.615088

bioRxiv · 10.1101/2024.09.26.615088

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

Tallino, S.·Etebari, R.·McDonough, I.·Leon, H.·Sepulveda, I.·Winslow, W.·Bartholomew, S. K.·Perez, S.·Mufson, E. J.·Velazquez, R.

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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.

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Tallino, S., Etebari, R., McDonough, I., Leon, H., Sepulveda, I., Winslow, W., Bartholomew, S. K., Perez, S., Mufson, E. J., Velazquez, R.. 2024-09-27. Adult choline supplementation in a Down syndrome model reduces co-morbidities and improves cognition. https://doi.org/10.1101/2024.09.26.615088

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