The Neurobiology of Aging and Alzheimer Disease in Down Syndrome - Chapter 10: Genetics of Alzheimer’s disease in adults with Down syndrome

Elsevier, The Neurobiology of Aging and Alzheimer Disease in Down Syndrome, Volume , 1 January 2021
Lee J.H., Dang L.-H.T., Pang D., Krinsky-McHale S.J., Schupf N.

Down syndrome (DS) is one of the most common genetic diseases, and adults with DS show neuropathological signs of Alzheimer’s disease (AD) starting at age 40 years of age, and nearly one-half will develop dementia by age 60, owing to triplication and overexpression of the APP gene on chromosome 21. Beyond the amyloid precursor protein (APP) gene located on chromosome 21, it is necessary to examine other genes on chromosome 21 and genes outside chromosome 21 to explain the wide range of age at onset and phenotypic expression in adults with DS. To date, only a limited number of candidate gene studies and one genome-wide association study have been reported in adults with DS. Here, we discuss the advantages of performing genetic studies in people with DS, and then discuss the role of reported genes that are known to be associated with AD risk in adults with DS or in the general population. Lastly, we discuss how future longitudinal multiomic and imaging study can enhance our understanding of the biology of AD.