Apolipoprotein E ε4 genotype status is not associated with neuroimaging outcomes in a large cohort of HIV+ individuals

Abstract

Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in HIV-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes) and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM) and basal ganglia) were examined. Secondary analyses explored this relationship separately in individuals ≥ 50 years old (n= 173) and < 50 years old (n=63). No significant differences were observed between ApoE ε4+ (ApoE ε3/ε4 & ApoE ε4/ε4) individuals (n=69) and ApoE ε4- (ApoE ε2/ε3 & ApoE ε3/ε3) individuals (n=167). When individuals were further divided by age, no significant genotype group differences were identified in individuals < 50 or ≥ 50 years of age on any neuroimaging outcome. The ApoE ε4 allele did not affect brain integrity in this large, diverse sample of HIV+ individuals. The effects of ApoE ε4 may not be apparent until more advanced ages, and may be more prominent when present along with other risk factors for neuronal damage.

HIV-associated neurocognitive disorder

“…Analysis of CHARTER and MACS participants found no association of APOE status with development of cognitive impairment, or with imaging abnormalities in either structural or metabolic brain imaging. [38–40] A major reservation about these cohort analyses is the relatively young age, which might limit the power to detect APOE4 effects. In another recent report, while APOE4 was again not associated with HAND, it was associated with abnormal CSF-abeta42 levels, consistent with increased risk of developing AD with further aging.…”

Fate of microglia during HIV‐1 infection: From activation to senescence?

“…Our understanding of amyloid metabolism during HIV-1 infection is further clouded by conflicting reports on the association between HAND development and Apolipoprotein E (ApoE) expression, which is a significant risk factor for abnormal amyloid deposition resulting in sporadic AD development (Kim et al, 2009;Morris et al, 2010). While some early reports demonstrate increased frequencies of HAD development in ApoE carriers, more recent studies do not find a correlation between ApoE phenotype and HAND development characterized by either neurocognitive impairments or detrimental neuroimaging outcomes (Burt et al, 2008;Cooley et al, 2016;Corder et al, 1998;Morgan et al, 2013;Valcour et al, 2004b). These differential results could be due to disparities in stages of neurocognitive impairments examined (HAD vs. milder forms of HAND) or in ages of study subjects since ApoE was shown to be an independent risk factor for HAD in HIV-infected patients who are 50 year of age and older, but not in younger subjects (Valcour et al, 2004a).…”

ApoE ε4 Is Associated With Cognition, Brain Integrity, and Atrophy in HIV Over Age 60

“…One such report from the CHARTER group (mean age = 40 years, 25% over age 50 years) finds no difference in HAND prevalence between ApoE ε4 carriers and non-carriers nor did they identify neuroimaging differences by carrier status. 19,20 Similarly, investigations from the Multicenter AIDS Cohort Study (MACS, with mean ages at enrollment across groups between 30 to 40 years) do not identify an impact of ApoE ε4 on development of cognitive impairment among participants who tested normal at baseline. 21 One group carefully tested the hypothesis that age may influence the association between ApoE ε4 carrier status and cognitive outcomes using data from the National NeuroAIDS Tissue Consortium (NNTC) noting detrimental effects on HAND diagnosis, executive functioning and information processing in older age (> 50 years) but not in those of younger age.…”