Impact of apolipoprotein E ?4 and HIV on cognition and brain atrophy: antagonistic pleiotropy and premature brain aging.

ABSTRACT:

Objective

The apolipoprotein E (APOE) ?4 allele may accelerate the progression of HIV disease, and increase the risk for developing HIV-associated neurocognitive disorder (HAND). Whether APOE?4 allele(s) and age may influence brain atrophy in HIV patients is unknown and was evaluated.

Methods

Automated morphometry on magnetic resonance images, using FreeSurfer analyses, neuropsychological testing and APOE genotyping were performed in 139 subjects [70 seronegative controls (SN); 69 clinically-stable HIV subjects].

Results

Compared to SN, HIV subjects had smaller volumes throughout the brain regardless of their HAND status. Compared to APOE?4- subjects, SN controls with APOE?4 had better memory and larger global brain volumes (cerebral white matter and cortex) while HIV subjects with the APOE?4 allele(s) had poorer cognition (verbal fluency, learning, executive function and memory) and smaller cerebral and cerebellar white matter and subcortical structures. Further stratification of age showed that younger (<50 years) APOE?4+SN subjects had larger putamen and cerebral white matter, while younger APOE?4+HIV subjects had poorer performance on verbal fluency and smaller brain volumes [3-way (HIV-status×APOE?4×Age) interaction-p-values=0.005 to 0.03].

Interpretation

These findings suggest that APOE?4 allele(s) may show antagonistic pleiotropy on cognition and brain atrophy in SN controls, but may lead to premature aging with neurodegeneration in younger HIV patients prior to the development of HAND. Potential mechanisms for such interactions may include stronger neuro-inflammation or greater amyloid deposition in younger HIV subjects with APOE?4 allele(s). Early screening for the APOE?4 allele and brain atrophy with morphometry may guide neuroprotective intervention of cognitively normal HIV subjects prior to the development of HAND. Longitudinal follow-up studies and larger sample sizes are needed to validate these cross-sectional results.

SUBMITTER: Chang L 

PROVIDER: S-EPMC3171637 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature