Single nucleotide polymorphisms in aquaporin-4 associate with cognitive impairment status in people with HIV

AbstractNeurocognitive impairments are more frequent in people with HIV (PWH) compared to their uninfected counterparts. HIV-associated neurocognitive disorder (HAND) is a spectrum disorder and up to 50% of PWH are reported to suffer from HAND. Altered waste clearance  from the brain, chronic neuroinflammation and impaired metabolic processes may contribute to abnormal aging in PWH and are more common among those who suffer from HAND. Thus, it is important to identify earlier predictors for development of HAND. A key contributor to cognitive impairment in HIV an d in Alzheimer’s disease (AD) is formation and accumulation of aberrant proteins including hyperphosphorylated Tau (pTau). Previous data from AD and traumatic brain injury studies report that impaired waste clearance from the brain contributes in part to cognitive impairments. Evidence suggests th at theaquaporin 4 (aqp4) gene may have an important role in waste clearance from the brain as single nucleotide polymorphisms (SNPs) inaqp4 have been reported to associate with changes in cognitive decline in AD patients. Given some similarities between HAND and AD, we assessed potential associations of severalaqp4 SNPS with cognitive impairment in PWH. Our data show that homozygous carriers of the minor allele in SNPs rs3875089 and rs3763040 had significantly lower neuropsychological test Z-scores in multiple domains compared to the other genotypes. Interestingly, this decrease in Z-scores was only observed in PWH and no...

Source: Journal of NeuroVirology - May 16, 2023 Category: Neurology Source Type: research