14-3-3 Protein in CSF reflects SIV-mediated pre-synaptic damage

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• HIV-associated neurocognitive disorders (HAND) persist despite combined anti-retroviral therapy (cART).
• Cognitive decline correlates with reduced synaptic and dendritic density.
• Early detection of synaptic damage is crucial for understanding HAND pathogenesis.

Purpose of the Study:

• To characterize the appearance of the neuronal damage marker 14-3-3 protein in CSF during SIV infection.
• To determine if CSF 14-3-3 levels reflect synaptic alterations in the brain.
• To investigate the relationship between CSF 14-3-3, synaptic proteins, and viral load in the CNS.

Main Methods:

• SIV-inoculated macaques were studied over a 3-month infection course.
• Cerebrospinal fluid (CSF) was analyzed for 14-3-3 protein.
• Cortical grey matter was examined for levels of pre-synaptic (synaptophysin) and post-synaptic (PSD-95) proteins.
• SIV RNA levels in the CNS were quantified.

Main Results:

• SIV-infected macaques with 14-3-3 in CSF showed significantly lower levels of the pre-synaptic protein synaptophysin.
• Synaptophysin levels were inversely correlated with SIV RNA in the CNS.
• CSF 14-3-3 levels did not correlate with PSD-95 levels or brain viral replication.

Conclusions:

• The presence of 14-3-3 protein in CSF during asymptomatic SIV infection signifies pre-synaptic damage.
• CSF 14-3-3 may serve as an early biomarker for synaptic alterations in HAND.
• Targeting pre-synaptic damage could be a therapeutic strategy for HAND.