Human Total Tau and its Role as a Possible Biomarker for Cognitive Deficits in Cerebral Malaria

Abstract

Cerebral malaria (CM) caused by Plasmodium falciparum infection is a major cause of death in children of developing countries, yet the costs of CM are not just death alone. Recent studies have indicated that children who survive the disease have an increased risk of persistent neurological deficits and cognitive impairments. In this study we investigated the cerebral spinal fluid (CSF) levels of the protein tau as a potential predicative measure of the severity of these deficits. Tau is associated with the stabilization and assembly of neuronal microfilaments and is found in the CSF after neuron damage. Elevated levels of tau have been found in children with CM. We hypothesized that levels of tau in CM children would be higher in those children who had neurologic deficits and higher in those who had long-term cognitive impairments, compared to those who did not. We measured tau in the CSF of 142 CM Ugandan children and compared levels to the children’s cognitive and neurologic test scores in areas such as working memory, executive attention and learning. Working memory was negatively correlated to tau levels at both time of enrollment and at six months later (P=0.01 rho=-0.3; P=0.02 rho=-0.3). Executive attention and learning were not correlated to tau levels (all P>0.05), and there was no significant difference between those children who had neurologic deficits and those who did not (P=0.5). Investigations of tau levels with cognitive impairments are ongoing, as cognitive testing is still being performed on some children.