Chapter 11

Role of APP in the Pathophysiology of Down Syndrome and Alzheimer’s Disease

Kumar Sambamurti, Miguel A. Pappolla, Debomoy K. Lahiri, Nigel H. Greig, Panneerselvam Chinnakannu, Ann-Charlotte Granholm and Vasudevaraju Padmaraju

Abstract

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.

Total Pages: 249-272 (24)

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