Increase in β-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome

Abstract

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- _ (A _ ) 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 _ peptides, as well as total A _ 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 _ in CSF during early childhood of DS patients observed in this study are probably due to the trisomy of the A _ precursor APP, which leads to an overproduction of A _ . Despite the increased CSF concentrations of A _ , 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 _ pathology preceding tau pathology in AD

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