Impairment of the RE-1-silencing transcription factor (REST) and REST-dependent genes in Down Syndrome (DS) neuronal progenitor cells and neurospheres has been published recently. As dysregulation of this system has been shown at the RNA level and considering the long and unpredictable way from RNA to proteins, and as it is the proteins that do the function in brain, we decided to test this hypothesis at the protein level. Cortex of brains of patients with Down Syndrome at the early second trimester were used. REST-dependent structures as synapsin I, brain derived neurotrophic factor BDNF and neuronal growth-associated protein SCG10 were determined at the protein level using immunoblotting. Proteins were comparably expressed in fetal Down syndrome and control brains. Even when normalized versus housekeeping genes (glyceraldehyde-6-phosphate-dehydrogenease) and a marker for neuronal density (neuron-specific enolase) DS results were resembling controls. Therefore, we cannot confirm the REST-hypothesis by our studies in the 18/19th week of gestation at the protein level in brain and taking into account that the hypothesis was based upon studies in progenitor cells.