APOE ε4 allele and CSF APOE on Cognition in HIV-Infected Subjects

The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE epsilon 4 allele(s) in HIV-infected patients are unknown. However, APOE epsilon 4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE epsilon 4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (-19%, p = 0.03). While SN subjects with or without epsilon 4 allele showed no difference in CSF APOE levels, epsilon 4+ HIV+ subjects had similar levels to the SN subjects but higher levels than epsilon 4- HIV+ subjects (+34%, p = 0.01). Furthermore, while HIV+ subjects with epsilon 2 or epsilon 3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r = +0.35, p = 0.05), epsilon 4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r = -0.61, p = 0.02), had lower Global Cognitive Scores (r = -0.57, p = 0.03), and had poorer performance on tests involving learning (epsilon 4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in epsilon 4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the epsilon 4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.