What is the pathophysiology of Alzheimer disease (AD) in Down syndrome (DS)?

Updated: Nov 13, 2019
  • Author: Norberto Alvarez, MD; Chief Editor: Jasvinder Chawla, MD, MBA  more...
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The reason why Alzheimer disease (AD) is more frequent in individuals with Down syndrome (DS) is not known. All recognized mutations for AD are associated with increased deposition of amyloid beta (Abeta), a peptide fragment comprising 39-43 amino acids that derives from the catabolism of the amyloid precursor protein (APP) molecule. The discovery that the APP gene is on the 21st chromosome [23] led to the hypothesis that the early and universal development of AD pathology is due to a third copy of the APP gene. Nonetheless, many steps in the amyloid cascade hypothesis remain unproven.

The Abeta peptide has been found in the brains of children with DS as young as 8 years, and the deposits increase with age. Interestingly, despite the extensive deposits in the brain, there is no linear correlation with AD. There is a gap between the presence of abnormal brain pathology and the early signs of AD, suggesting that other factors (genetic or environmental) may play an important role in the development of AD.

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