What can babies with Down syndrome possibly tell us about Alzheimer’s dementia in adults?

It may seem paradoxical to focus on babies when attempting to understand a disease only apparent in adulthood, but I have always argued that the only way to understand a phenotypic endpoint at the neural, cognitive, behavioural or environmental levels is to trace its developmental trajectory from infancy onwards.  By age 30, 100% of individuals with Down syndrome (DS) present with the amyloid-beta plaque brain pathology of Alzheimer’s disease, because of the trisomy of the APP gene on chromosome 21.  Yet not all of them go on to develop the clinical symptoms of dementia, despite life expectancy having increased significantly in recent decades.  What protects those who don’t?  The aim of the project that I will present during this talk is to identify, already in infancy, individual differences in DS that might explain the protective and risk factors for subsequent dementia, by comparing the study of infants with DS, over a very broad genetic, cellular, neural, behavioural and environmental protocol, with the study of adults with DS who do or do not have Alzheimer’s disease.

     Karmiloff-Smith, A. (1998) Development itself is the key to understanding developmental disorders. Trends in Cognitive  Sciences, 2(10), 389-398.

     Karmiloff-Smith, A., D’Souza, D., Dekker, T.M., Van Herwegen, J., Xu, F., Rodic, M. & Ansari, D. (2012).  Genetic and environmental vulnerabilities in children with neurodevelopmental disorders.   PNAS, 109, 2, 17261–17265.

     Steele, A., Scerif, G., Cornish, K., & Karmiloff-Smith, A. (2013). Learning to read in Williams syndrome and Down syndrome: syndrome-specific precursors and developmental trajectories. Journal of Child Psychology and Psychiatry, 54, 754–762.

     Karmiloff-Smith, A. (2013). Challenging the use of adult neuropsychological models for explaining neurodevelopmental disorders: Developed versus developing brains. The Quarterly Journal of Experimental Psychology, 66, 1–14.