title: APOE ε 4 allele and CSF APOE on cognition in HIV-infected subjects.
abstract: 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 ε 4 allele(s) in HIV-infected patients are unknown. However, APOE ε 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 ε 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 ε 4 allele showed no difference in CSF APOE levels, ε 4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε 4- HIV+ subjects (+34%, p= 0.01). Furthermore, while HIV+ subjects with ε 2 or ε 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), ε 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 (ε 4 allele x [APOE] interaction, p = 0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε 4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε 4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.
authors.affiliation: Pacific Biosciences Research Center, University of Hawaii, 1993 East-West Road, Honolulu, HI 96822, USA. marilou@pbrc.hawaii.edu
authors.forename: Marilou A
authors.initials: MA
authors.lastname: Andres
authors.forename: Ute
authors.initials: U
authors.lastname: Feger
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
authors.forename: Sody
authors.initials: S
authors.lastname: Munsaka
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Jiang
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
mesh_terms: D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000235:genetics*; D000483:Alleles; D053327:Apolipoprotein E4 / Q000134:cerebrospinal fluid* / Q000235:genetics*; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid* / Q000235:genetics; D003071:Cognition; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020033:Protein Isoforms / Q000134:cerebrospinal fluid / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020033:Protein Isoforms