TY - JOUR
T1 - Cerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers
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 B.
AU - Morgello, Susan
AU - Cherner, Mariana
AU - Grant, Igor
AU - Achim, Cristian L.
PY - 2012/11/28
Y1 - 2012/11/28
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.
AB - 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.
KW - HIV dementia
KW - apolipoprotein E
KW - b-amyloid
KW - neurofibrillary pathology
KW - phospho-Tau
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UR - http://www.scopus.com/inward/citedby.url?scp=84870242810&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e32835a117c
DO - 10.1097/QAD.0b013e32835a117c
M3 - Article
C2 - 23018443
AN - SCOPUS:84870242810
SN - 0269-9370
VL - 26
SP - 2327
EP - 2335
JO - AIDS
JF - AIDS
IS - 18
ER -