title: 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 human immunodeficiency virus (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 and ApoE ε4/ε4) individuals (n = 69) and ApoE ε4- (ApoE ε2/ε3 and 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.
authors.affiliation: University of Missouri - St. Louis, St. Louis, MO, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Cooley
authors.affiliation: University of Missouri - St. Louis, St. Louis, MO, USA.|Missouri Institute of Mental Health, St. Louis, MO, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Paul
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Morgan
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Deng
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Jie Ashley
authors.initials: JA
authors.lastname: Chen
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Ellis
authors.affiliation: Washington University in St. Louis, Box 8111 660 South Euclid Ave, Saint Louis, MO, 63110, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: University of Washington, Seattle, Seattle, WA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: University of Washington, Seattle, Seattle, WA, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: University of California, San Diego, San Diego, CA, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: Washington University in St. Louis, Box 8111 660 South Euclid Ave, Saint Louis, MO, 63110, USA. ancesb@neuro.wustl.edu.
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics*; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D005838:Genotype; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D015658:HIV Infections / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D012307:Risk Factors; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053327:Apolipoprotein E4
keywords: Brain volumetrics; Genetics; HIV/AIDS; Magnetic resonance spectroscopy