Bastan Fatemeh, Saeedi-Moghaddam Fateme, Rashidian Maryam, Mirhosseini Fatemeh, Mozhgani Sayed-Hamidreza
Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran.
Department of Microbiology and Virology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
BMC Neurol. 2025 Nov 22;25(1):516. doi: 10.1186/s12883-025-04500-1.
Alzheimer's disease (AD) is the most common form of dementia worldwide. Human Herpesvirus 6 (HHV-6), a neurotropic virus capable of establishing lifelong latency in the CNS, has been suggested as a potential risk factor in the pathogenesis of AD. However, studies investigating this association have reported inconsistent findings. This systematic review and meta-analysis aimed to explore this association further and shed light on the matter.
This study aimed to systematically review and meta-analyze existing literature to assess the association between HHV-6 infection and the risk of Alzheimer's disease.
A comprehensive search of MEDLINE, Web of Science, EMBASE, and grey literature was conducted following PRISMA guidelines. Case-control studies that assessed the presence of HHV-6 in patients with Alzheimer's disease were included. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS), and meta-analysis was performed using RevMan 5.3 and STATA 17.0. Subgroup and sensitivity analyses were conducted to assess heterogeneity and robustness of the results. Publication bias was evaluated using funnel plots, trim-and-fill analysis, and Begg's test.
Eight case-control studies comprising 1,507 participants were included. The pooled analysis revealed a significant association between HHV-6 infection and increased risk of Alzheimer's [OR = 1.81, 95% CI: 1.16-2.84, p = 0.009], with moderate heterogeneity (I² = 60%). Sensitivity analysis excluding one outlier strengthened the association [OR = 2.78, 95% CI: 1.65-4.70] and eliminated heterogeneity (I² = 0%). Subgroup analyses demonstrated stronger associations in studies using PCR detection [OR = 2.20, 95% CI: 1.22-3.98] and brain tissue samples [OR = 2.49, 95% CI: 1.22-5.11], whereas serological and blood-based studies yielded weaker, non-significant associations. Publication bias was not detected.
This meta-analysis suggests that HHV-6 infection is significantly associated with an increased risk of Alzheimer's disease. Nevertheless, the exact causal mechanisms remain unclear. Further longitudinal and mechanistic studies are needed to better understand the role of HHV-6 in Alzheimer's pathogenesis and to evaluate potential antiviral options for preventive or therapeutic strategies.
阿尔茨海默病（AD）是全球最常见的痴呆形式。人疱疹病毒6型（HHV-6）是一种嗜神经病毒，能够在中枢神经系统中建立终身潜伏感染，已被认为是AD发病机制中的一个潜在危险因素。然而，调查这种关联的研究报告结果并不一致。本系统评价和荟萃分析旨在进一步探讨这种关联，并阐明这一问题。
本研究旨在系统评价和荟萃分析现有文献，以评估HHV-6感染与阿尔茨海默病风险之间的关联。
按照PRISMA指南对MEDLINE、科学网、EMBASE和灰色文献进行全面检索。纳入评估阿尔茨海默病患者中HHV-6存在情况的病例对照研究。使用纽卡斯尔-渥太华量表（NOS）评估研究质量，并使用RevMan 5.3和STATA 17.0进行荟萃分析。进行亚组分析和敏感性分析以评估结果的异质性和稳健性。使用漏斗图、修剪填充分析和Begg检验评估发表偏倚。
纳入了8项病例对照研究，共1507名参与者。汇总分析显示HHV-6感染与阿尔茨海默病风险增加之间存在显著关联[比值比（OR）=1.81，95%置信区间（CI）：1.16-2.84，p=0.009]，异质性中等（I²=60%）。排除一个离群值的敏感性分析加强了这种关联[OR=2.78，95%CI：1.65-4.70]并消除了异质性（I²=0%）。亚组分析表明，在使用聚合酶链反应（PCR）检测的研究[OR=2.20，95%CI：1.22-3.98]和脑组织样本的研究[OR=2.49，95%CI：1.22-5.11]中关联更强，而血清学和基于血液的研究产生的关联较弱且无统计学意义。未检测到发表偏倚。
这项荟萃分析表明HHV-6感染与阿尔茨海默病风险增加显著相关。然而，确切的因果机制仍不清楚。需要进一步的纵向和机制研究，以更好地了解HHV-6在阿尔茨海默病发病机制中的作用，并评估预防性或治疗性策略的潜在抗病毒选择。
