University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR U1219, F-33000, Bordeaux, France.
University of Bordeaux, CNRS-UMR 5234 and CHU Bordeaux, Virology Department, F-33000, Bordeaux, France.
Transl Psychiatry. 2021 Jul 31;11(1):414. doi: 10.1038/s41398-021-01532-2.
While previous studies suggest the implication of herpes simplex virus (HSV) in the onset of Alzheimer's disease (AD), no study has investigated its association with early neuroimaging markers of AD. In the Three-City and the AMI cohorts, the associations between HSV infection and (i) hippocampal volume (n = 349), (ii) white matter alterations in the parahippocampal cingulum and fornix using diffusion tensor imaging (n = 260), and (iii) incidence of AD (n = 1599) were assessed according to APOE4 status. Regardless of APOE4 status, infected subjects presented (i) significantly more microstructural alterations of the parahippocampal cingulum and fornix, (ii) lower hippocampal volumes only when their anti-HSV IgG level was in the highest tercile-reflecting possibly more frequent reactivations of the virus (p = 0.03 for subjects with a high anti-HSV IgG level while there was no association for all infected subjects, p = 0.19), and (iii) had no increased risk of developing AD. Nevertheless, among APOE4 carriers, infected subjects presented lower hippocampal volumes, although not significant (p = 0.09), and a two or three times higher risk of developing AD (adjusted Hazard ratio (aHR) = 2.72 [1.07-6.91] p = 0.04 for infected subjects and aHR = 3.87 [1.45-10.28] p = 0.007 for infected subjects with an anti-HSV IgG level in the highest tercile) while no association was found among APOE4 noncarriers. Our findings support an association between HSV infection and AD and a potential interaction between HSV status and APOE4. This reinforces the need to further investigate the infectious hypothesis of AD, especially the associated susceptibility factors and the possibility of preventive treatments.
虽然先前的研究表明单纯疱疹病毒（HSV）与阿尔茨海默病（AD）的发病有关，但尚无研究调查其与 AD 的早期神经影像学标志物之间的关联。在三城和 AMI 队列中，根据 APOE4 状态，评估了 HSV 感染与 (i) 海马体积（n=349）、(ii) 海马旁扣带回和穹窿的白质改变（n=260），以及 (iii) AD 发病率（n=1599）之间的关系。无论 APOE4 状态如何，感染组的 (i) 海马旁扣带回和穹窿的微观结构改变更明显，(ii) 海马体积更小，仅当他们的抗 HSV IgG 水平处于最高三分位时-可能反映病毒更频繁的再激活（高抗 HSV IgG 水平的受试者 p=0.03，而所有感染受试者没有关联，p=0.19），以及 (iii) 没有增加患 AD 的风险。然而，在 APOE4 携带者中，感染组的海马体积较小，尽管无统计学意义（p=0.09），且患 AD 的风险增加两到三倍（感染组的调整后 HR=2.72[1.07-6.91]，p=0.04，感染组中抗 HSV IgG 水平最高三分位的 HR=3.87[1.45-10.28]，p=0.007），而在 APOE4 非携带者中未发现关联。我们的研究结果支持 HSV 感染与 AD 之间的关联，以及 HSV 状态和 APOE4 之间的潜在相互作用。这加强了进一步研究 AD 的传染性假说的必要性，特别是相关的易感性因素和预防性治疗的可能性。
