DISTRIBUTION OF N-ACETYLASPARTYLGLUTAMATE IMMUNOREACTIVITY IN HUMAN BRAIN AND ITS ALTERATION IN NEURODEGENERATIVE DISEASE

The dipeptide N-acetylaspartylglutamate (NAAG) may be involved in the process of glutamatergic signaling by both acting at glutamate recepto rs and as a glutamate protransmitter. In the present study we determin ed the cellular localization and distribution of NAAG-like immunoreact ivity (NAAG-LI) in normal human brain and in neurodegenerative disorde rs to ascertain the degree of NAAG's colocalization to putative glutam atergic pathways. Immunohistochemistry with an antibody against NAAG w as performed on control, Huntington's disease (HD) and Alzheimer's dis ease (AD) human autopsy and biopsy brain sections from the cerebral co rtex, hippocampus, amygdala, neostriatum, brainstem and spinal cord. I n normal human brain, NAAG-LI was widespread localized to putative glu tamatergic pyramidal neurons of the cerebral cortex and hippocampus. P unctate NAAG-LI was present in areas known to receive neuronal glutama tergic input, such as layer IV of the cerebral cortex, striatal neurop il, and the outer portion of the molecular layer of the hippocampal de ntate gyrus. In the two pathologic brain regions examined, the HD neos triatum and the AD temporal cortex, we observed a widespread loss of N AAG-LI neurons. In addition NAAG-LI reactive microglia surrounding pla ques were seen in AD temporal cortex but not in the HD striatum. Our r esults suggest that NAAG is substantially localized to putative glutam atergic pathways in human brain and that NAAG-LI neurons are vulnerabl e to the neurodegenerative process in HD and AD. (C) 1997 Elsevier Sci ence B.V.