Trisomy of chromosome 21 (Ts21), with duplication of one copy of all its
genes to increase its copy number by 0.5-fold, is well tolerated, allowing the birth of
live children. However, subjects with Ts21 suffer a spectrum of problems, including
intellectual disability, skeletal deformity, and a number of secondary conditions such as
defects in the visual system, hearing loss, cardiovascular disease, and a progressive
dementia similar to Alzheimer’s disease (AD). In this chapter, we discuss the genotypephenotype
relationships and identify the role played by individual genes. We also detail
the role of the amyloid β (A4) precursor protein causing AD in Ts21 individuals.
Keywords: Alzheimer’s disease, Amyloid, degradation, Down syndrome, gene
duplication, lysosome, protein processing.
