Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers

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 Gelman, Susan Morgello, Mariana Cherner, Igor Grant, Cristian L. Achim

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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-associate 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.

Original languageEnglish (US)
Pages (from-to)2327-2335
Number of pages9
JournalAIDS
Volume26
Issue number18
DOIs
StatePublished - Nov 28 2012

Fingerprint

Apolipoprotein E4
Amyloid
HIV
Alzheimer Disease
Odds Ratio
Genotype
Confidence Intervals
Neurocognitive Disorders
Brain
Biomarkers
Logistic Models
Immunohistochemistry
Alleles

Keywords

  • apolipoprotein E
  • b-amyloid
  • HIV dementia
  • neurofibrillary pathology
  • phospho-Tau

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Soontornniyomkij, V., Moore, D. J., Gouaux, B., Soontornniyomkij, B., Tatro, E. T., Umlauf, A., ... Achim, C. L. (2012). Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. AIDS, 26(18), 2327-2335. https://doi.org/10.1097/QAD.0b013e32835a117c

Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. / Soontornniyomkij, Virawudh; Moore, David J.; Gouaux, Ben; Soontornniyomkij, Benchawanna; Tatro, Erick T.; Umlauf, Anya; Masliah, Eliezer; Levine, Andrew J.; Singer, Elyse J.; Vinters, Harry V.; Gelman, Benjamin; Morgello, Susan; Cherner, Mariana; Grant, Igor; Achim, Cristian L.

In: AIDS, Vol. 26, No. 18, 28.11.2012, p. 2327-2335.

Research output: Contribution to journalArticle

Soontornniyomkij, V, Moore, DJ, Gouaux, B, Soontornniyomkij, B, Tatro, ET, Umlauf, A, Masliah, E, Levine, AJ, Singer, EJ, Vinters, HV, Gelman, B, Morgello, S, Cherner, M, Grant, I & Achim, CL 2012, 'Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers', AIDS, vol. 26, no. 18, pp. 2327-2335. https://doi.org/10.1097/QAD.0b013e32835a117c
Soontornniyomkij V, Moore DJ, Gouaux B, Soontornniyomkij B, Tatro ET, Umlauf A et al. Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. AIDS. 2012 Nov 28;26(18):2327-2335. https://doi.org/10.1097/QAD.0b013e32835a117c
Soontornniyomkij, Virawudh ; Moore, David J. ; Gouaux, Ben ; Soontornniyomkij, Benchawanna ; Tatro, Erick T. ; Umlauf, Anya ; Masliah, Eliezer ; Levine, Andrew J. ; Singer, Elyse J. ; Vinters, Harry V. ; Gelman, Benjamin ; Morgello, Susan ; Cherner, Mariana ; Grant, Igor ; Achim, Cristian L. / Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers. In: AIDS. 2012 ; Vol. 26, No. 18. pp. 2327-2335.
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AU - Soontornniyomkij, Virawudh

AU - Moore, David J.

AU - Gouaux, Ben

AU - Soontornniyomkij, Benchawanna

AU - Tatro, Erick T.

AU - Umlauf, Anya

AU - Masliah, Eliezer

AU - Levine, Andrew J.

AU - Singer, Elyse J.

AU - Vinters, Harry V.

AU - Gelman, Benjamin

AU - Morgello, Susan

AU - Cherner, Mariana

AU - Grant, Igor

AU - Achim, Cristian L.

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N2 - 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-associate 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.

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