Aging and Apolipoprotein E in HIV Infection

Abstract

With the implementation of increasingly effective antiretroviral therapy (ART) over the past three decades, individuals infected with HIV live a much longer life. HIV infection is no longer a terminal but rather a chronic disease. However, the lifespan of infected individuals remains shorter than that of their uninfected peers. Even with ART, HIV infection may potentiate “premature” aging. Organ-associated disease and systemic syndromes that occur in treated HIV-infection are like that of older, uninfected individuals. Brain aging may manifest as structural changes or neurocognitive impairment that are beyond the chronological age. The spectrum of neurological, cognitive, and motor deficiencies, currently described as HIV-associated neurocognitive disorders (HAND), may reflect earlier onset of mechanisms common to HIV infection and aging (accelerated aging). HAND could also reflect the neurological impact of HIV infection superimposed on comorbidities linked to age and chronic inflammation, leading to a higher prevalence of neurocognitive impairment across the age span (accentuated aging). In addition, apolipoprotein E (ApoE), one of the most influential host risk factors for developing Alzheimer’s disease, has been implicated in the development of HAND. But studies differ as to whether ApoE is relevant, and whether age and ApoE interact to impair brain function in the HIV-infected patient. What is clear is that HIV-infected individuals are living longer with HIV, and therefore factors related to aging and health need to be examined in the context of current, effective ART. This review addresses the recent evidence for the influence of aging and ApoE on HIV-associated neurocognitive impairment.Electronic supplementary materialThe online version of this article (10.1007/s13365-018-0660-2) contains supplementary material, which is available to authorized users.

The Genetic Variability of APOE in Different Human Populations and Its Implications for Longevity

“…Lastly, an interesting set of studies tried to investigate a link between APOE and the modulation of HIV infection as a chronic disease, now that the affected individuals can live to older ages thanks to anti-retroviral therapy. Even though the overall results are somewhat contrasting, isoform ε4 seems to correlate in different cases with the development of HIV-associated neurocognitive disorders, impaired cognition, dyslipidaemia, premature brain aging, and increased chance of debilitating opportunistic infections [116,117,118,119,120] (see also a comprehensive review in Reference [121]).…”

Risk Factors and Pathogenesis of HIV-Associated Neurocognitive Disorder: The Role of Host Genetics

“…HIV-infection accelerates and accentuates premature aging of the nervous system by potentiating, at least in part, immunological senescence, measured by the accumulation of CD28 − /CD57 + T cells [ 78 , 144 ] and activation of the monocyte markers CD163 and CXCL10 [ 145 ]. The neurocognitive performance of young (≤40 years of age) HIV+ patients was found to be equivalent to those of older (≥50 years of age) seronegative individuals [ 146 , 147 ].…”

“…Sections of temporal lobe/hippocampus, entorhinal cortex and frontal lobes from the brains of HIV-1 infected patients obtained at autopsy were immunohistochemically stained with antibodies against Aβ and phosphorylated-tau (p-tau) [ 149 , 153 ]. In contrast to the neuritic Aβ plaques observed in the AD brain, diffusely distributed Aβ plaques and sparsely-scattered neurofibrillary lesions were detected in both HIV cases and non-HIV controls [ 144 ]. Those features correlated with aging rather than symptomatic AD.…”

Brain amyloid in virally suppressed HIV-associated neurocognitive disorder

“…11 APOE genotyping was conducted in only one study. 8 While APOE4 status has been associated with HAND in some studies 12,13 this has not always been replicated, 14 although this result may be influenced by cohorts that included PLHIV of relatively young age, who were not virally suppressed and clinically stable. 14 Nevertheless, APOE4 status is a major risk factor for AD and other dementias 14 and, thus, remains relevant in aging PLHIV cohorts that could be at higher risk of coincidental AD.…”