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 ε4 allele(s) in HIV-infected patients are unknown. However, APOE ε4 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 ε4 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 ε4 allele showed no difference in CSF APOE levels, ε4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε4− HIV+ subjects (+34%, p = 0.01). Furthermore, while HIV+ subjects with ε2 or ε3 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), ε4+ 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 (ε4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.