Transfer of the amyloid β and/or of β-amyloid precursor protein of the fetus with trisomy 21 to the maternal blood stream and its possible contribution to the pathogenesis of the maternal Alzheimer’s Disease

Abstract

Down Syndrome (DS) is the most frequent genetic pathology. It affects 1 out of every 800 newborn babies. Approximately between a 90% and a 95% of all the cases of DS are attributed to a trisomy in chromosome 21. One of the genes contained in this chromosome is the gene of β-amyloid precursor protein (βAPP). The metabolism of this protein yields, among others, the amyloid beta peptides made up of 40 amino acids (Aβ40) and 42 amino acids (Aβ42). The evidence that is derived from several sources – genetic, among them – suggests that the Aβ participates in the pathogenesis of Alzheimer’s Disease (AD).It is worth pointing at the fact that the transfer of cells, extracellular chromosomal material and some proteins from the fetus to the mother and vice versa has been widely described. The transfer rate from the fetus to the mother is higher when the mother is carrying a baby with trisomy 21. This has led to the hypothesis that sets forth that during the gestation of a baby with DS there is a greater fetomaternal transfer of cells and of products of the genes of chromosome 21 – among them, βAPP and its metabolites Aβ40 and Aβ42. It is possible to speculate on the possible contribution of the fetal components – among them, Aβ – to the higher risk of suffering AD, which has been reported in a subpopulation of women who have given birth to children with DS. On the other hand, the detection of the βAPP – mainly intracellular – and of the β amyloid peptides in maternal blood and urine during the early stages of gestation could be taken as a potential non invasive biochemical prenatal marker of DS.