N-ACETYLASPARTYLGLUTAMATE, N-ACETYLASPARTATE, AND N-ACETYLATED ALPHA-LINKED ACIDIC DIPEPTIDASE IN HUMAN BRAIN AND THEIR ALTERATIONS IN HUNTINGTON AND ALZHEIMER-DISEASES

There is mounting evidence, primarily from research in experimental an imals, that the dipeptide N-acetylaspartylglutamate (NAAG) and its cat abolic enzyme, N-acetylated alpha-linked acid dipeptidase (NAALADase), are involved in glutamatergic neurotransmission. Previous studies in neuropsychiatric disorders associated with the dysregulation of glutam atergic neurotransmission, such as schizophrenia, seizure disorders, a nd amyotrophic lateral sclerosis (ALS), have revealed. region-specific alterations in the levels of NAAG and in the activity of NAALADase. T o establish better the cellular localization of these and related para meters in human brain, we have examined their alterations in two well- characterized selective neurodegenerative disorders, Huntington Diseas e (HD) and Alzheimer Disease (AD). Brain regions from postmortem contr ols and HD-or AD-affected individuals were assayed to determine the ac tivity of NAALADase as well as the levels of NAAG, N-acetylaspartate ( NAA), and several amino acids. The relationships between changes in th ese neurochemical parameters and changes in neuronal and glial cell de nsity were determined. The present report demonstrates that the decrea ses in the levels of NAAG and NAA and in the activity of NAALADase in AD and HD brain correlate primarily with neuronal loss. BY inference, the results suggest that NAAG and NAA have primarily a neuronal locali zation in human brain and that there is a close relationship between N AAG and the dipeptidase NAALADase in populations of affected neurons.