HIV disease duration, but not active brain infection, predicts cortical amyloid beta deposition.
HIV disease duration, but not active brain infection, predicts cortical amyloid beta deposition.
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DOI：
10.1097/qad.0000000000002893
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发表时间：
2021-07-15
期刊：
影响因子：
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通讯作者：
Crary JF
中科院分区：
文献类型：
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作者：
Morgello S;Cortes EP;Gensler G;Meloni G;Jacobs MM;Murray J;Borukov V;Crary JF
抗微生物肽淀粉样蛋白β（Aβ）的异常沉积是阿尔茨海默病（AD）的特征。本研究的目的是阐明人类免疫缺陷病毒（HIV）和其他嗜神经病原体富集队列中脑Aβ的风险因素。横断面队列研究。我们检查了257名供体的尸检大脑，平均年龄为52.8岁; 62%为男性; 194名为HIV+，63名为HIV-。通过免疫组织化学鉴定了额区和颞区的过度磷酸化tau（p-tau）和Aβ。进行APOE基因分型。在单变量分析中确定Aβ的临床和神经病理学预测因子，然后在多变量回归中进行检验。在32%的样本中发现了皮质Aβ，在27%的样本中发现了活动性脑感染。随着年龄的增长和具有APOE ε4等位基因，Aβ的几率增加;对于整个样本，HIV+状态是保护性的，脑部感染不是预测因子。在HIV阳性人群中，Aβ的预测因子是HIV病程和APOE等位基因，而不是年龄。当将HIV病程和其他HIV参数引入整个样本的模型时，HIV病程相当于年龄作为Aβ的预测因子。我们假设，HIV免疫抑制和刺激的双重方面，以及老年HIV+个体中有益的存活效应，解释了HIV+状态降低和HIV持续时间增加，Aβ的几率。重要的是，对于HIV，疾病持续时间取代年龄成为Aβ的独立风险，这表明HIV相关的大脑衰老加速。
Abnormal deposition of the antimicrobial peptide amyloid beta (Aβ) is a characteristic of Alzheimer’s Disease (AD). The objective of this study was to elucidate risk factors for brain Aβ in a cohort enriched for human immunodeficiency virus (HIV) and other neurotropic pathogens. Cross-sectional cohort study. We examined autopsy brains of 257 donors with a mean age of 52.8 years; 62% were male; and 194 were HIV+ and 63 HIV-. Hyperphosphorylated tau (p-tau) and Aβ were identified in frontal and temporal regions by immunohistochemistry. APOE genotyping was performed. Clinical and neuropathological predictors for Aβ were identified in univariate analyses, and then tested in multivariate regressions. Cortical Aβ was identified in 32% of the sample, and active brain infection in 27%. Increased odds of Aβ were seen with increasing age and having an APOE ε4 allele; for the overall sample, HIV+ status was protective and brain infection was not a predictor. Within the HIV+ population, predictors for Aβ were duration of HIV disease and APOE alleles, but not age. When HIV disease duration and other HIV parameters were introduced into models for the entire sample, HIV disease duration was equivalent to age as a predictor of Aβ. We hypothesize that dual aspects of immune suppression and stimulation in HIV, and beneficial survivor effects in older HIV+ individuals, account for HIV+ status decreasing, and HIV duration increasing, odds of Aβ. Importantly, with HIV, disease duration replaces age as an independent risk for Aβ, suggesting HIV-associated accelerated brain senescence.