Viral lots and CD4 cell counts were assessed at the same time the cognitive screening was performed, as described (McArthur et al. in individuals with lower CD4 cell counts and higher viral lots. We provide details of an assay which may possess diagnostic, prognostic, or restorative implications for individuals with HAND. Active viral replication may be needed to travel the immune response against Tat protein, but this powerful immune response against the protein may be neuroprotective. Keywords: neurotoxicity, neurovirology, dementia, neuroprotection, glutamate, neutralizing antibodies Intro HIV infects glial cells and may establish a reservoir within the brain. Infected cells in the brain can launch neurotoxic viral proteins, including the HIV transactivator protein, Tat (Tornatore et al. 1994a; Tornatore et al. 1994b). The arrival of highly active antiretroviral therapy (HAART) offers successfully decreased the incidence of HIV dementia by decreasing viral weight, thus enabling the recovery of CD4+ T cells and repairing immunity (Sacktor et al. 2001). However, the prevalence of HIV-associated neurocognitive disorders (HAND) is actually increasing, because individuals on HAART are living longer (Dore et al. 2003; Neuenburg et al. 2002; Sacktor 2002; Sacktor et al. 2002; Simpson TNFSF8 et al. 2003). Once proviral DNA is definitely formed, HAART fails to target the early viral proteins. Of these proteins, Tat is released extracellularly, where it is highly neurotoxic and may be transferred along neuronal pathways to cause neuronal injury at distant sites. It interacts with glial cells to induce activation and launch of neurotoxic factors, leading to common damage. (Rumbaugh and Nath 2006). Interestingly, some individuals by no means develop HAND despite severe immune suppression and high viral lots. This suggests that sponsor susceptibility genes play an important part in the neuropathogenesis of this condition. The effect of variations in chemokines and cytokines likely reflects the importance of a host-generated inflammatory cascade (Gonzalez et al. 2002; Quasney et al. 2001). Another probability is that variations in the hosts Emeramide (BDTH2) adaptive immune response impact susceptibility to HAND. For example, the ability of the sponsor to produce neutralizing antibodies to Tat may impact Tats ability to cause neurotoxicity. This may possess important implications for development of a vaccine strategy to treat or prevent HIV dementia and additional neurological complications of HIV illness. It is therefore imperative to monitor levels of antibodies to viral proteins within the CNS, as both diagnostic and prognostic markers. HIV infection is unique in that detection of disease or antibody to disease in the spinal fluid is not regarded as diagnostic of Emeramide (BDTH2) viral invasion of the CNS, whereas analysis of additional common viral encephalitides, such as Herpes simplex encephalitis, require detection of disease or virus specific antibodies within the CNS. Earlier studies have attempted to detect viral proteins and their transcripts within the CNS of infected individuals, but have Emeramide (BDTH2) not verified effective for quantitation due to lack of level of sensitivity (Hudson et al. 2000; Kruman et al. 1999; Trujillo et al. 1996; Westendorp et al. 1995; Wiley et al. 1996). Tat antibodies have not previously been analyzed in CSF. MATERIALS AND METHODS Study samples CSF samples used were from Northeastern AIDS Dementia (NEAD) cohort, Johns Hopkins Oxidative Stress cohort, and National NeuroAIDS Cells Consortium (NNTC). Viral lots and CD4 cell counts were assessed at the same time the cognitive screening was performed, as explained (McArthur et al. 2004). HIV-infected samples were from individuals classified by Memorial Sloan Kettering (MSK) scale as individuals with no cognitive impairment (MSK=0, n=15), with slight cognitive impairment (MSK=0.5C1, n=20), and with moderate cognitive impairment (MSK2, n=17). The HIV-infected Emeramide (BDTH2) individuals in this study showed no correlation between their neurocognitive status and their blood and CSF viral lots and CD4 cell counts. Thus, correlations which we demonstrate based on neurocognitive status should not be confounded by viral weight or immune status. Control organizations included individuals with additional neuro-inflammatory or neuro-infectious diseases (n=8) and non-inflammatory controls (normal pressure hydrocephalus, n=5). These individuals did not possess risk factors for HIV illness. All samples had been centrifuged prior to storage, hence only cell free CSF was used. Table 1 provides a summary of.