Linard Morgane, Garrigue Isabelle, Vellas Bruno, Coley Nicola, Zetterberg Henrik, Blennow Kaj, Ashton Nicholas James, Payoux Pierre, Salabert Anne-Sophie, Dartigues Jean-François, Mazere Joachim, Andrieu Sandrine, Helmer Catherine
INSERM U1219 Bordeaux Population Health Research Center, University of Bordeaux, 146, rue Léo Saignat, 33076, Bordeaux Cedex, France.
CNRS, MFP, UMR 5234, University of Bordeaux, Bordeaux, France.
Sci Rep. 2025 Jan 18;15(1):2362. doi: 10.1038/s41598-024-84583-x.
In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan. Plasma Aβ42/40 ratio, neurofilament light chain and p-tau181 were also available for a sub-sample of participants. Multivariate linear regressions were performed and stratified by APOE4 genotype. The median age was 74.0 years, 85.2% were infected with HSV-1. Infected participants tended to have a lower cortical amyloid load than uninfected participants (β = -0.08, p = 0.06), especially those suspected of reactivating HSV-1 most frequently (i.e. with a high anti-HSV-1 IgG level; n = 58, β = -0.09 p = 0.04). After stratification, the association was only significant in APOE4 carriers (n = 43, β = -0.21 p = 0.01). No association was found with the plasma biomarkers. The trend toward lower cortical amyloid load in HSV-1-infected participants was unexpected given the pre-existing literature and may be explained either by a modified immune response in HSV-1 infected subjects which could favour the clearance of amyloid deposits or by a selection bias.
体外和动物研究表明，接种单纯疱疹病毒1型（HSV-1）可导致淀粉样蛋白沉积、tau蛋白过度磷酸化和/或神经元丢失。在此，我们研究了人类中HSV-1与阿尔茨海默病生物标志物之间的关联。我们的样本包括182名来自多领域阿尔茨海默病预防试验的有认知衰退风险的参与者，他们进行了HSV-1血浆血清学检测和淀粉样蛋白PET扫描。部分参与者的子样本还提供了血浆Aβ42/40比值、神经丝轻链和p-tau181数据。进行了多变量线性回归，并按APOE4基因型进行分层。中位年龄为74.0岁，85.2%的人感染了HSV-1。感染的参与者皮质淀粉样蛋白负荷往往低于未感染的参与者（β = -0.08，p = 0.06），尤其是那些最常疑似HSV-1重新激活的参与者（即抗HSV-1 IgG水平高；n = 58，β = -0.09，p = 0.04）。分层后，这种关联仅在APOE4携带者中显著（n = 43，β = -0.21，p = 0.01）。未发现与血浆生物标志物有关联。鉴于既往文献，HSV-1感染参与者皮质淀粉样蛋白负荷较低的趋势出乎意料，这可能是由于HSV-1感染受试者的免疫反应改变有利于淀粉样蛋白沉积的清除，或者是由于选择偏倚所致。
