Department of Psychiatry.
Department of Pathology, University of California San Diego, La Jolla, California, USA.
AIDS. 2020 Jun 1;34(7):1001-1007. doi: 10.1097/QAD.0000000000002506.
HIV-associated neurocognitive disorders (HAND) persist despite the widespread implementation of combined antiretroviral therapy (ART). As people with HIV (PWH) age on ART regimens, the risk of age-related comorbidities, such as Alzheimer's disease may increase. However, questions remain as to whether HIV or ART will alter such risks. Beta amyloid (Aβ) and phosphorylated-tau (p-tau) proteins are associated with Alzheimer's disease and their levels are altered in the CSF of Alzheimer's disease cases.
To better understand how these Alzheimer's disease-related markers are affected by HIV infection and ART, postmortem CSF collected from 70 well characterized HIV+ decedents was analyzed for Aβ1-42, Aβ1-40, and p-tau levels.
Aβ1-42 and Aβ1-40 CSF levels were higher in cases that were exposed to ART. Aβ1-42 and Aβ1-40 CSF levels were also higher in cases on protease inhibitors compared with those with no exposure to protease inhibitors. Aβ1-42 and Aβ1-40 levels in CSF were lowest in HIV+ cases with HIV-associated dementia (HAD) and levels were highest in those diagnosed with asymptomatic neurocognitive impairment (ANI) and minor neurocognitive disorder (MND). Aβ1-42 and Aβ1-40 were inversely related with p-tau levels in all cases, as previously reported.
These data suggest that ART exposure is associated with increased levels of Aβ1-42 and Aβ1-40 in the CSF. Also, HAD, but not ANI/MND diagnosis is associated with decreased levels of Aβ1-42 and Aβ1-40 in CSF, potentially suggesting impaired clearance. These data suggest that HIV infection and ART may impact pathogenic mechanisms involving Aβ1-42 and Aβ1-40, but not p-tau.
尽管广泛实施了联合抗逆转录病毒疗法（ART），但仍存在与 HIV 相关的神经认知障碍（HAND）。随着接受 ART 治疗的 HIV 感染者（PWH）年龄的增长，与年龄相关的合并症（如阿尔茨海默病）的风险可能会增加。然而，关于 HIV 或 ART 是否会改变这些风险仍存在疑问。β淀粉样蛋白（Aβ）和磷酸化 tau 蛋白（p-tau）与阿尔茨海默病有关，其水平在阿尔茨海默病病例的脑脊液中发生改变。
为了更好地了解 HIV 感染和 ART 如何影响这些与阿尔茨海默病相关的标志物，分析了从 70 名特征明确的 HIV 阳性死者死后收集的脑脊液中 Aβ1-42、Aβ1-40 和 p-tau 水平。
暴露于 ART 的病例中 Aβ1-42 和 Aβ1-40 的 CSF 水平更高。与未接触蛋白酶抑制剂的病例相比，接触蛋白酶抑制剂的病例的 Aβ1-42 和 Aβ1-40 CSF 水平也更高。HIV 相关痴呆（HAD）的 HIV 阳性病例的 Aβ1-42 和 Aβ1-40 脑脊液水平最低，无症状神经认知障碍（ANI）和轻度神经认知障碍（MND）诊断的病例水平最高。如先前报道的那样，Aβ1-42 和 Aβ1-40 与所有病例的 p-tau 水平呈负相关。
这些数据表明，ART 暴露与 CSF 中 Aβ1-42 和 Aβ1-40 水平升高有关。此外，与 HAD 相关，而不是与 ANI/MND 诊断相关，与 CSF 中 Aβ1-42 和 Aβ1-40 水平降低有关，可能表明清除受损。这些数据表明，HIV 感染和 ART 可能会影响涉及 Aβ1-42 和 Aβ1-40 的致病机制，但不影响 p-tau。
