HIV-associated neurocognitive disorders (HAND) remain prevalent despite effective combined anti-retroviral
therapy (cART). Cognitive function has been shown to inversely correlate with decreased synaptic and dendritic density.
In this study, macaques inoculated with SIV were examined over a 3-month course of infection to characterize the
appearance of the neuronal damage marker 14-3-3 protein in CSF and to determine whether CSF 14-3-3 levels directly
reflected synaptic alterations. SIV-infected macaques with 14-3-3 in CSF had significantly lower levels of the presynaptic
protein synaptophysin in cortical grey matter. Synaptophysin levels were inversely correlated with amount of
SIV RNA in the CNS. In contrast, levels of 14-3-3 in CSF did not correspond with either alterations in levels of the postsynaptic
protein PSD-95 or viral replication in the brain. These findings suggest that the appearance of 14-3-3 in CSF
during asymptomatic infection reflects pre-synaptic damage in SIV-infected macaques and thus may serve as a marker of
the early synaptic alterations that underlie HIV-induced neurocognitive impairment.
Keywords: 14-3-3, CSF, HIV, PSD-95, SIV, synaptophysin.
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Published on: 22 September, 2013
Page: [281 - 287]