Trisomy 21 in patients with DS results in increased activity of an important antioxidant enzyme Cu/Zn superoxide dismutase (SOD) which gene is located on the 21st chromosome along with other proteins such as transcription factor Ets-2, stress inducing factors (DSCR1) and precursor of beta-amyloid protein responsible for the formation of amyloid plaques in Alzheimer disease.
Strong ets-2 immunoreactivity was observed in DS/AD and sporadic AD brains associated with degenerative markers such as bax, intracellular Abeta, and hyperphosphorylated tau.
We conclude that ETS2 is a transcriptional regulator of beta-APP and that overexpression of ETS2 in DS may play a role in the pathogenesis of the brain abnormalities in DS and possibly AD.
Because a small region of chromosome 21 containing the ets-2 gene is duplicated in patients with Alzheimer's disease, as well as in karyotypically normal Down syndrome, duplication of a subsection of the critical segment of chromosome 21 that is duplicated in Down syndrome may be the genetic defect in Alzheimer's disease.