Down Syndrome

Down syndrome (DS) is caused by an extra copy of the long arm of human chromosome 21 (HSA21) and the increased expression, due to dosage, of HSA21 encoded genes. In addition to intellectual disability, all individuals with DS develop the neuropathology of Alzheimer’s Disease (AD) by age 30-40. The amyloid precursor protein gene, APP, that is mutated or duplicated in some familial AD (FAD), is encoded by HSA21, over expressed in DS, and a candidate for causing AD in DS. However, only half of those with DS will develop the AD-like dementia by age 50-60, suggesting that additional HSA21 genes may modulate the effects of APP triplication, and/or protect the DS brain from early onset progression to dementia in spite of neuropathology. Familial Alzheimer’s Disease (FAD) is rare, accounting for fewer than 5% of all cases of AD, and is characterized by early onset, at <60 years of age. Mutations causing FAD have been identified in three genes, the amyloid precursor protein, APP, and the presenilin genes 1 and 2, PSEN1 and PSEN2. Down syndrome (DS), trisomy of human chromosome 21 (HSA21), is caused by an extra copy of all or part of the long arm of HSA21 and the increased expression, due to dosage, of some subset of HSA21 encoded genes. In addition to intellectual disability, all individuals with DS develop a neuropathology by the age of 30-40 similar to that seen in AD and approximately 50% will eventually develop an AD-like dementia by the age of 50-60. HSA21 encodes 161 classical protein coding genes of diverse functions, plus approximately 45 genes encoding keratin associated proteins (some proportion of which may be pseudogenes), five microRNA genes, and more than 300 genes/gene structures of completely unknown functions.

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Last date updated on April, 2024