title: Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers.
abstract: OBJECTIVE
  The apolipoprotein E (APOE) ε4 allele enhances cerebral accumulation of β-amyloid (Aβ) and is a major risk factor for sporadic Alzheimer's disease. We hypothesized that HIV-associated neurocognitive disorders (HAND) would be associated with the APOE ε4 genotype and cerebral Aβ deposition.
  
  
  METHODS
  Clinicopathological study of HIV-infected adults from four prospective cohorts in the US National NeuroAIDS Tissue Consortium.
  
  
  METHODS
  We used multivariable logistic regressions to model outcomes [Aβ plaques (immunohistochemistry) and HAND (standard criteria)] on predictors [APOE ε4 (allelic discrimination assay), older age (≥50 years), Aβ plaques, and their two-way interactions] and comorbid factors.
  
  
  RESULTS
  Isocortical Aβ deposits generally occurred as diffuse plaques and mild-to-moderate amyloid angiopathy. Isocortical phospho-Tau-immunoreactive neurofibrillary lesions were sparse. The APOE ε4 and older age were independently associated with the presence of Aβ plaques [adjusted odds ratio (OR) 10.16 and 5.77, 95% confidence interval (CI) 2.89 - 35.76 and 1.91-17.48, P = 0.0003 and 0.0019, respectively, n = 96]. The probability of HAND was increased in the presence of Aβ plaques among APOE ε4 carriers (adjusted OR 30.00, 95% CI 1.41-638.63, P = 0.029, n = 15), but not in non-ε4 carriers (n = 57).
  
  
  CONCLUSIONS
  The APOE ε4 and older age increased the likelihood of cerebral Aβ plaque deposition in HIV-infected adults. Generally, Aβ plaques in HIV brains were immunohistologically different from those in symptomatic Alzheimer's disease brains. Nonetheless, Aβ plaques were associated with HAND among APOE ε4 carriers. The detection of APOE ε4 genotype and cerebral Aβ deposition biomarkers may be useful in identifying living HAND patients who could benefit from Aβ-targeted therapies.
authors.affiliation: HIV Neurobehavioral Research Program and California NeuroAIDS Tissue Network, USA.
authors.forename: Virawudh
authors.initials: V
authors.lastname: Soontornniyomkij
authors.forename: David J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Ben
authors.initials: B
authors.lastname: Gouaux
authors.forename: Benchawanna
authors.initials: B
authors.lastname: Soontornniyomkij
authors.forename: Erick T
authors.initials: ET
authors.lastname: Tatro
authors.forename: Anya
authors.initials: A
authors.lastname: Umlauf
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Levine
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Mariana
authors.initials: M
authors.lastname: Cherner
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.forename: Cristian L
authors.initials: CL
authors.lastname: Achim
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy; D056344:Executive Function; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4