Synaptosomal proteins, beta-soluble N-ethylmaleimide-sensitive factor attachment protein (beta-SNAP), gamma-SNAP and synaptotagmin 1 in brain of patients with Down syndrome and Alzheimer's disease

Although it is well-known that synaptosomal proteins are deranged in neurod egenerative disorders, no information is available at the protein-chemical level as mainly immunochemical or immunohistochemical data were reported pr eviously. We therefore investigated synaptosomal proteins in brain specimen s from patients with Down syndrome (DS) and Alzheimer's disease (AD) to cha llenge the DS synaptic pathology as well as the relevance of DS to AD in sy naptic pathology. For the aim of this study, we employed two-dimensional el ectrophoresis and matrix-associated laser desorption ionization mass spectr oscopy and determined beta -soluble N-ethylmaleimide-sensitive factor attac hment protein (beta -SNAP), gamma -SNAP and synaptotagmin 1 (STT I) in 7 in dividual brain regions of controls and patients with DS and AD. In DS brain , beta -SNAP was significantly reduced in temporal cortex (p < 0.01). STT I (p65) and STT I (pI 7.0) were significantly reduced in thalamus (p < 0.01 and p < 0.05, respectively). In AD brain, <beta>-SNAP was significantly dec reased in temporal cortex (p < 0.05). STT I (p65) was significantly reduced in cerebellum (p < 0.05), and temporal (p < 0.001) and parietal cortex (p < 0.01). STT I (pl 7.0) was significantly reduced in temporal (p < 0.001) a nd parietal cortex (p < 0.01) and thalamus (p < 0.01), <gamma>-SNAP did not show any change in both DS and AD. The findings may explain impaired synap togenesis in DS and AD brain, which is well documented in DS brain already early in life, and/or synaptosomal loss secondary to neuronal loss observed in both neurodegenerative disorders. It may also represent, reflect or acc ount for the impaired neuronal transmission in DS and AD, caused by deterio ration of the exocytic machinery. Here, we provide evidence for several der anged synaptosomal proteins in several brain regions at the protein level i ndicating deficient synaptosomal wiring of the brain in DS and AD. Copyrigh t (C) 2001 S. Karger AG, Basel.