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. 2006 Apr 5;9(2):209–217. doi: 10.1111/j.1750-3639.1999.tb00219.x

Cortical Synaptic Density is Reduced in Mild to Moderate Human Immunodeficiency Virus Neurocognitive Disorder

IP Everall 1, RK Heaton 2,1, TD Marcotte 2,1, RJ Ellis 3,1, JA McCutchan 4,1, JH Atkinson 6,1, I Grant 6,1, M Mallory 3,1, E Masliah 3,5,✉; HNRC Group1
PMCID: PMC8098484  PMID: 10219738

Abstract

Dendritic and synaptic damage (without frank neuronal loss) may be seen in milder human immunodeficiency virus (HIV)‐related cognitive disorders. Synapse volume estimates, performed by stereological methods, could enhance the ability to detect subtle neuronal changes that may accompany cognitive impairment in HIV infection. For the present study, synaptic density and neuronal number were assessed by combined stereology/confocal microscopy and these measures were then correlated with ante‐mortem levels of cognitive performance in AIDS patients. Three‐dimensional stereological measures showed a significant correlation between reduced synaptic density and poor neuropsychological performance. To evaluate the specificity of any observed associations, additional variables including viral burden, astrogliosis and number of calbindin‐immunoreactive neurons were measured. Factor analysis of a set of neuropathological variables revealed two factors; one defined by synaptic density and volume fraction, calbindin pyramidal neuronal densities and viral burden; the second by astrocytosis and calbindin interneuron density. Only the first factor correlated significantly with neuropsychological functioning during life.

It is concluded that a combination of factors including synaptic damage, specific neuronal loss and increasing viral load underlies HIV‐associated cognitive impairment. As synaptic damage is potentially reversible, early diagnosis and treatment of mild cogntive disorders may improve functioning and prevent the progression of brain disease.

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The San Diego HIV Neurobehavioral Research Center (HNRC) group is affiliated with the University of California, San Diego, the Naval Hospital, San Diego, and the San Diego VA Medical Center, and includes: Igor Grant, MD, Director; J. Hampton Atkinson, MD, Co‐Director; Thomas D. Marcotte, PhD., Center Manager; James L. Chandler, MD. and Mark R. Wallace, MD, Co‐Investigators Naval Hospital San Diego; J. Allen McCutchan, MD, P.I. Neuromedical Component; Stephen A. Spector, MD, P.I. Virology Component; Robert K. Heaton, PhD., P.I. Neurobehavioral Component; Terry Jernigan, PhD and John Hesselink, MD, Co‐P.I.s Imaging Component; Eliezer Masliah, MD, P.I. Neuropathology Component; J. Allen McCutchan, MD, J. Hampton Atkinson, MD, and Ronald J. Ellis, MD, PhD, Clinical Trials Component; Daniel R. Masys, MD, P.I. Data Management Component; Ian Abramson, PhD, P.I. Statistics Unit; Julie Nelson, BA, Data Manager.

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