Drebrin, located in the dendritic spines of the neuron, plays a role in the synaptic plasticity together with actin filaments. Although drebrin regulates the morphological changes of spines in neurodegenerative disease such as Alzheimer's disease (AD), drebrin in Down syndrome (DS) showing AD-like neuropathology has not been studied. We used Western blotting to determine protein levels of drebrin and F-actin in frontal, temporal cortex and cerebellum from patients with DS and AD as compared to controls. A monoclonal antibody against drebrin and F-actin was used. Drebrin levels were significantly decreased in frontal (means +/- standard deviation; DS 0.24 +/- 0.52; AD 0.16 +/- 0.14; controls 2.56 +/- 3.48) and temporal cortex (DS 0.07 +/- 0.11; AD 0.07 +/- 0.15; controls 1.71 +/- 1.51) and drebrin was also decreased when normalized with F-actin. No changes were observed in cerebellum. Decreased drebrin could not simply be due to cell loss (F-actin) or neuronal loss (comparable neuron-specific enolase between groups). Reduced drebrin could be responsible for or representing the loss of spine plasticity in DS and may be a useful indicator for the impaired arborization in neurodegenerative disorders.