Neurological Syndromes Associated with Anti-GAD Antibodies

Int J Mol Sci. 2020 May 24;21(10):3701. doi: 10.3390/ijms21103701.


Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.

Keywords: GAD65 autoimmunity; autoimmune epilepsy; cerebellar ataxia; glutamic acid decarboxylase; limbic encephalitis; neuronal antibodies; paraneoplastic neurological syndromes; stiff-person syndrome.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases of the Nervous System / diagnosis
  • Autoimmune Diseases of the Nervous System / immunology*
  • Autoimmune Diseases of the Nervous System / therapy
  • Autoimmunity*
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / immunology
  • Cerebellar Ataxia / therapy
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Limbic Encephalitis / diagnosis
  • Limbic Encephalitis / immunology
  • Limbic Encephalitis / therapy
  • Neurons / enzymology*
  • Neurons / immunology
  • Stiff-Person Syndrome / diagnosis
  • Stiff-Person Syndrome / immunology
  • Stiff-Person Syndrome / therapy


  • Glutamate Decarboxylase
  • glutamate decarboxylase 2