Increase in beta-amyloid levels in cerebrospinal fluid of children with down syndrome

Background: Individuals with Down syndrome (DS) invariably develop Alzheimer's disease ( AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid-beta (A beta) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change over time. The first CSF sample was taken at 8 months and the following two samples at 20-40 and 54 months of age. Results: Individual levels of the A beta peptides, as well as total A beta levels in CSF increased over time when measured with Western blot. Tau in CSF decreased whereas there was no change in levels of phosphorylated tau over time. Conclusion: The increasing levels of A beta in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the A beta precursor APP, which leads to an overproduction of A beta. Despite the increased CSF concentrations of A beta, there were no signs of an AD-indicating tau pattern in CSF, since the levels of total tau decreased and phosphorylated tau remained unchanged. This observation further strengthens the theory of A beta pathology preceding tau pathology in AD. Copyright (c) 2007 S. Karger AG, Basel.