Document Detail


Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers.
MedLine Citation:
PMID:  23018443     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
DESIGN: 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).
CONCLUSION: 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:
Virawudh Soontornniyomkij; David J Moore; Ben Gouaux; Benchawanna Soontornniyomkij; Erick T Tatro; Anya Umlauf; Eliezer Masliah; Andrew J Levine; Elyse J Singer; Harry V Vinters; Benjamin B Gelman; Susan Morgello; Mariana Cherner; Igor Grant; Cristian L Achim
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  26     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-06-03     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  2327-35     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
AIDS Dementia Complex / metabolism,  pathology*
Adult
Aged
Alzheimer Disease / metabolism,  pathology*
Amyloid beta-Peptides / metabolism*
Apolipoprotein E4 / genetics*,  metabolism
Brain / metabolism,  pathology*
Cerebral Amyloid Angiopathy
Executive Function
Female
Genotype
HIV Infections / metabolism,  pathology*
Humans
Immunohistochemistry
Logistic Models
Male
Middle Aged
Multivariate Analysis
Odds Ratio
Predictive Value of Tests
Prospective Studies
Risk Factors
Grant Support
ID/Acronym/Agency:
P30 MH062512/MH/NIMH NIH HHS; P30 MH062512/MH/NIMH NIH HHS; P50 AG016570/AG/NIA NIH HHS; P50 AG016570/AG/NIA NIH HHS; P50 DA026306/DA/NIDA NIH HHS; P50 DA026306/DA/NIDA NIH HHS; P50 MH045294/MH/NIMH NIH HHS; R01 AG043384/AG/NIA NIH HHS; R01 MH062962/MH/NIMH NIH HHS; R03 DA027513/DA/NIDA NIH HHS; R03 DA027513/DA/NIDA NIH HHS; R24 MH059724/MH/NIMH NIH HHS; R24 MH059724/MH/NIMH NIH HHS; R24 MH059745/MH/NIMH NIH HHS; R24 MH059745/MH/NIMH NIH HHS; R24 NS038841/NS/NINDS NIH HHS; R24 NS038841/NS/NINDS NIH HHS; R24 NS045491/NS/NINDS NIH HHS; R24 NS045491/NS/NINDS NIH HHS; R25 MH081482/MH/NIMH NIH HHS; R25 MH081482/MH/NIMH NIH HHS; U01 AI035040/AI/NIAID NIH HHS; U01 AI035040/AI/NIAID NIH HHS; U01 MH008021/MH/NIMH NIH HHS; U01 MH083500/MH/NIMH NIH HHS; U01 MH083501/MH/NIMH NIH HHS; U01 MH083501/MH/NIMH NIH HHS; U01 MH083506/MH/NIMH NIH HHS; U01 MH083506/MH/NIMH NIH HHS; U01 MH083507/MH/NIMH NIH HHS; U01 MH083507/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Apolipoprotein E4
Comments/Corrections

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