Cystathionine disappearance with neuronal loss: a possible neuronal marker

Cystathionine is an important intermediate in the transsulfuration pathway of methionine catabolism and is normally present in high concentration in the human CNS. We have measured the concentration of cystathionine, other amino acids, and brain proteins in the cerebral cortex, cerebellar cortex and spinal cord of two cases with ceroid lipofuscinosis. Neuropathological and biochemical studies of Case 1, at an advanced stage, Case 2, at an early stage, and five controls were correlated with clinical and neurological findings. The concentration of an unidentified 54,000 Dalton protein was greatly increased in Case 1 as observed by 2-D gel electrophoresis. Neurons and cystathionine were almost totally absent from the cortex and cerebellum of Case 1, while they were slightly reduced in Case 2, in comparison to control brains. These studies suggest that cystathionine may be specifically located within neurons. We present for the first time the observation that there was a strikingly low brain concentration of cystathionine, a potential neuronal marker, in an advanced stage of a neurodegenerative process.