Expression of proteins linked to exocytosis and neurotransmission in patients with Creutzfeldt-Jakob disease

In order to characterize synaptic involvement in human spongiform encephalo pathies, the expression of synaptic vesicle-associated proteins, synaptophy sin and synapsin-l, and presynaptic plasma membrane proteins, synaptosomal- associated protein of 25 kDa (SNAP-25) and syntaxin-1, was examined in the brains of four patients who had suffered from sporadic Creutzfeldt-Jakob di sease. Nerve cell loss, spongiform degeneration, astrocytosis, and depositi on of prion protein (PrP) were observed in the cerebral cortex in every cas e. Decreased immunoreactivity for synaptophysin, synapsin-l, SNAP-25, and s yntaxin-1 was observed in the cerebral cortex in every case, thus showing g eneralized reduction of proteins involved in exocytosis of synaptic vesicle s in the brains of patients with spongiform encephalopathy. Upregulation of synaptophysin and SNAP-25, a feature associated with PA4 deposits in Alzhe imer's disease (AD), was not observed in association with PrP deposition. T he present results indicate that synaptic pathology is a major event in spo ngiform encephalopathy, and suggest that synaptic loss, together with neuro n loss and selective involvement of certain populations of local-circuit ne urons, as shown in other studies, may account for the dramatic neurological decay and for the main neurological symptoms in patients with CJD. (C) 199 9 Academic Press.