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N-acetylaspartylglutamate,N-acetylaspartate, andN-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer diseases

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Molecular and Chemical Neuropathology

Abstract

There is mounting evidence, primarily from research in experimental animals, that the dipeptideN-acetylaspartylglutamate (NAAG) and its catabolic enzyme,N-acetylated α-linked acid dipeptidase (NAALADase), are involved in glutamatergic neurotransmission. Previous studies in neuropsychiatric disorders associated with the dysregulation of glutamatergic neurotransmission, such as schizophrenia, seizure disorders, and amyotrophic lateral sclerosis (ALS), have revealed region-specific alterations in the levels of NAAG and in the activity of NAALADase. To establish better the cellular localization of these and related parameters in human brain, we have examined their alterations in two well-characterized selective neurodegenerative disorders, Huntington Disease (HD) and Alzheimer Disease (AD). Brain regions from postmortem controls and HD- or AD-affected individuals were assayed to determine the activity of NAALADase as well as the levels of NAAG,N-acetylaspartate (NAA), and several amino acids. The relationships between changes in these neurochemical parameters and changes in neuronal and glial cell density were determined. The present report demonstrates that the decreases 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 localization in human brain and that there is a close relationship between NAAG and the dipeptidase NAALADase in populations of affected neurons.

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Authors and Affiliations

  1. Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Charlestown, MA

    Lucius A. Passani, Ruth E. Carter & Joseph T. Coyle

  2. Laboratory for Molecular Neuropathology, Massachusetts General Hospital, Charlestown, MA

    Jean Paul G. Vonsattel

  3. The Consolidated Department of Psychiatry, Harvard Medical School, McLean Hospital, 115 Mill Street, 02178, Belmont, MA

    Lucius A. Passani, Ruth E. Carter & Joseph T. Coyle

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  1. Lucius A. Passani
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  2. Jean Paul G. Vonsattel
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  4. Joseph T. Coyle
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Correspondence to Joseph T. Coyle.

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Passani, L.A., Vonsattel, J.P.G., Carter, R.E. et al. N-acetylaspartylglutamate,N-acetylaspartate, andN-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer diseases. Molecular and Chemical Neuropathology 31, 97–118 (1997). https://doi.org/10.1007/BF02815236

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