Neurovirological correlation with HIV-associated neurocognitive disorders and encephalitis in a HAART-era cohort.

Objective: Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. SUBJECTS AND ASSAYS: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens.

The National NeuroAIDS Tissue Consortium brain gene array: two types of HIV-associated neurocognitive impairment.

Background: The National NeuroAIDS Tissue Consortium (NNTC) performed a brain gene expression array to elucidate pathophysiologies of Human Immunodeficiency Virus type 1 (HIV-1)-associated neurocognitive disorders.

Methods: Twenty-four human subjects in four groups were examined A) Uninfected controls; B) HIV-1 infected subjects with no substantial neurocognitive impairment (NCI); C) Infected with substantial NCI without HIV encephalitis (HIVE); D) Infected with substantial NCI and HIVE. RNA from neocortex, white matter, and neostriatum was processed with the Affymetrix® array platform.

Prefrontal dopaminergic and enkephalinergic synaptic accommodation in HIV-associated neurocognitive disorders and encephalitis.

Unlabelled: Changes in synapse structure occur in frontal neocortex with HIV encephalitis (HIVE) and may contribute to HIV-associated neurocognitive disorders (HAND). A postmortem survey was conducted to determine if mRNAs involved in synaptic transmission are perturbed in dorsolateral prefrontal cortex (DLPFC) in subjects with HIVE or HAND. Expression of the opioid neurotransmitter preproenkephalin mRNA (PENK) was significantly decreased in a sampling of 446 brain specimens from HIV-1 infected people compared to 67 HIV negative subjects.

Persistent hijacking of brain proteasomes in HIV-associated dementia.

Immunoproteasome induction sustains class 1 antigen presentation and immunological vigilance against HIV-1 in the brain. Investigation of HIV-1-associated alterations in brain protein turnover by the ubiquitin-proteasome system was performed by (1) determining proteasome subunit changes associated with persistent brain inflammation due to HIV-1; (2) determining whether these changes are related to HIV-1 neurocognitive disturbances, encephalitis, and viral loads; and (3) localizing proteasome subunits in brain cells and synapses. On the basis of neurocognitive performance, virological, and immunological measurements obtained within 6 months before death, 153 autopsy cases were selected.

Abnormal striatal dopaminergic synapses in National NeuroAIDS Tissue Consortium subjects with HIV encephalitis.

People with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) have neurological problems that overlap with diseases associated with abnormal dopaminergic (DAergic) synaptic transmission, including subcortical dementia, motor slowing, psychosis, and drug addiction. Previous study has suggested that DAergic tone may be decreased in HIV/AIDS, but biochemical confirmation of that tenet is still lacking. To that end, this study addresses the neurochemical interaction between HIV infection and DAergic synaptic transmission in human brain specimens.

Potential role for white matter lysosome expansion in HIV-associated dementia.

Expansion of the lysosomal apparatus occurs in subcortical white matter in brains from persons with AIDS. This study examined whether HIV-associated subcortical dementia (HAD) is significantly related to this lysosomal anomaly. Brain cortex and adjacent white matter from the middle frontal gyrus were obtained from the National NeuroAIDS Tissue Consortium.

Acquired neuronal channelopathies in HIV-associated dementia.

A gene expression profile of the human brain cortex was performed in people with HIV-1-associated dementia (HAD) using Affymetrix HG-U133 chips. Messenger RNA transcripts in middle frontal gyrus from subjects with HAD or milder neurocognitive dysfunction were compared to HIV-negative people. The analysis focused on ionic conductance carriers that control membrane excitation.

Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV.

We examined the interrater (IRR) of clinical ratings of neuropsychological (NP) impairment and neurocognitive diagnoses in HIV. Thirty participants with advanced HIV-infection who were enrolled in a multicenter HIV brain banking research project underwent comprehensive NP and neuromedical evaluations. Using a standardized system of guidelines, neuropsychologists from six participating sites independently assigned clinical ratings of NP impairment, as well as multilevel diagnoses reflecting the inferred etiology of the impairments and their effects on everyday functioning.