Apolipoprotein e4, cognition, and behavior in youth with Down syndrome

Abstract

Given the early emergence of Alzheimer’s disease (AD) related pathology in Down syndrome (DS; Trisomy 21), it is possible that changes may be evident in childhood or adolescence in Apolipoprotein (APOE) e3/e4 or e4/e4 genotypes in relation to e3/e3 genotypes. Given findings of early involvement of striatum amyloid beta (Aβ) peptide deposition in DS, we propose that a profile of executive and inhibitory control dysfunction will be found in youth carrying the risk e4 allele. From a pool of 72 children and adolescents with DS we examined a sub-sample with the risk e4 allele (n = 8; e3/e4) and without the risk e4 allele (n = 8; e3/e3). Participants were matched for age and ethnicity (range 8 - 21 years; mean age 14 years). Karyotypes were gathered from medical records, confirming a diagnosis of Trisomy 21. We collected genetic information (Oragene saliva kit) in home; they were sent to the Emory Biomarker Service Center to determine genotypes. We administered the Kaufman Brief Intelligence Test (KBIT-2) and a set of cognitive outcomes measures validated for Down syndrome, the Arizona Cognitive Test Battery. Results from the KBIT-2 indicated no significant differences in verbal raw score (p = 0.65), non-verbal raw score (p = 0.69), or intelligence quotient (IQ) (p = 0.32). Neuropsychological test scores did differ; with poorer performance in the e4 sample on the CANTAB Paired Associates Learning task (p = 0.05) and parent/caregiver reports of working memory (p = 0.08). Therefore, as early as adolescence some changes may be seen in e4 carriers.