Supplementary Material for: Blood Biomarkers of Neuronal/Axonal and Glial Injury in Human Immunodeficiency Virus-Associated Neurocognitive Disorders

<b><i>Introduction:</i></b> Approximately half of the people living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HANDs). However, the neuropathogenesis of HAND is complex, and identifying reliable biomarkers has been challenging. <b><i>Methods:</i></b> This study included 132 participants aged 50 and older from greater San Diego County. The participants were divided into three groups: PLWH with HAND (<i>n</i> = 29), PLWH without HAND (<i>n</i> = 73), and seronegatives without cognitive impairment (<i>n</i> = 30). Peripheral blood was collected at the clinical assessment, and plasma levels of neurofilament light chain (NfL), phosphorylated Tau 181 (pTau181), and glial fibrillary acidic protein (GFAP) were measured by enzyme-linked immunosorbent assay (ELISA). <b><i>Results:</i></b> Plasma levels of NfL (but not pTau181 and GFAP) were significantly associated with HAND at a medium effect size (<i>p</i> = 0.039, Cohen’s <i>d</i> = 0.45 for HAND + vs. HAND−). Notably, higher levels of NfL were significantly associated with HAND diagnosis even after adjusting for sex. <b><i>Discussion:</i></b> Our data suggest that neuronal degeneration (as evidenced by increased levels of NfL), but not tau pathology or glial degeneration, is related to cognitive status in PLWH. Our results corroborate the view that blood NfL is a promising biomarker of cognitive impairment in PLWH.

<b><i>引言：</i></b> 约半数人类免疫缺陷病毒感染者（PLWH，people living with HIV）会罹患HIV相关神经认知障碍（HAND，HIV-associated neurocognitive disorders）。然而HAND的神经发病机制复杂，可靠生物标志物的识别颇具挑战。
<b><i>方法：</i></b> 本研究纳入了来自大圣地亚哥县的132名50岁及以上受试者，分为三组：伴HAND的HIV感染者组（<i>n</i> = 29）、不伴HAND的HIV感染者组（<i>n</i> = 73），以及无认知障碍的血清学阴性对照组（<i>n</i> = 30）。在临床评估时采集外周血，通过酶联免疫吸附试验（ELISA，enzyme-linked immunosorbent assay）检测血浆中神经丝轻链（NfL，neurofilament light chain）、磷酸化tau蛋白181（pTau181，phosphorylated Tau 181）以及胶质纤维酸性蛋白（GFAP，glial fibrillary acidic protein）的水平。
<b><i>结果：</i></b> 血浆NfL水平（而非pTau181与GFAP）与HAND存在显著关联，效应量中等（HAND+组 vs HAND-组：<i>p</i> = 0.039，科恩<i>d</i> = 0.45）。值得注意的是，即便校正性别因素后，较高的NfL水平仍与HAND诊断显著相关。
<b><i>讨论：</i></b> 本研究数据表明，HIV感染者的认知状态与神经元变性（以NfL水平升高为佐证）相关，而与tau病理或胶质变性无关。本研究结果进一步证实，血液NfL是HIV感染者认知障碍的潜在可靠生物标志物。