To the Editor.
—The pathogenesis of acquired immunodeficiency syndrome (AIDS) dementia complex is controversial. Since no neuronal localization of human immunodeficiency virus (HIV) has been shown, it has been hypothesized that soluble factors, produced from infected macrophages, glial cells, or directly by the virus, might target the neurons and induce apoptotic cell death, resulting in brain atrophy and dementia. In vitro and in vivo experiments indicate that the viral proteins gp 120 and Tat may cause neuronal apoptosis, which can be blocked by antagonists of N-methyl-D-aspartate (NMDA) and non-NMDA receptors.1-3 This evidence suggests that the glutamatergic system and excitotoxicity are involved in the pathogenesis of AIDS dementia complex. However, viral proteins do not bind to glutamate receptors: therefore, overstimulation of glutamate receptors seems to be mediated by interactions with endogenous glutamate or other excitatory amino acid receptor agonists. In fact, the toxic effect of gp 120 was prevented
Ferrarese C, Riva R, Dolara A, De Micheli A, Frattola L. Elevated Glutamate in the Cerebrospinal Fluid of Patients With HIV Dementia. JAMA. 1997;277(8):630. doi:10.1001/jama.1997.03540320032030