Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders.

TitlePolyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders.
Publication TypeJournal Article
Year of Publication2014
AuthorsMerali, S, Barrero, CA, Sacktor, NC, Haughey, NJ, Datta, PK, Langford, D, Khalili, K
JournalJ AIDS Clin Res
Date Published2014

OBJECTIVES: Spermidine/spermine-N-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIV-associated neurocognitive disorders.METHODS: Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity.RESULTS: Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p<0.0001) and between MCMD and NCI and ANI (p<0.0001). studies suggest that the HIV protein Tat may be responsible in part for astrocyte-derived acetyl polyamine release.INTERPRETATION: Our data suggest that polyamine metabolism may play a pivotal role in the neurodegeneration process among HAND patients. Changes in polyamine flux may serve as a potential predictive diagnostic biomarker for different severities of HAND.

Alternate JournalJ AIDS Clin Res
PubMed ID25893137
PubMed Central IDPMC4397651
Grant ListHHSN271201000030C / MH / NIMH NIH HHS / United States
N01MH22005 / MH / NIMH NIH HHS / United States
P30 MH092177 / MH / NIMH NIH HHS / United States
R01 DA033213 / DA / NIDA NIH HHS / United States