Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimer's Disease: A Population-Based Cohort Study

Abstract IntroductionHerpes Simplex Virus 1 (HSV1) is a neuroinvasive virus capable of entering the brain which makes it a candidate pathogen for increasing risk of dementia. Previous studies are inconsistent in their findings regarding the link between HSV1 and dementia, therefore, we investigated how HSV1 relates to cognitive decline and dementia risk using data from a population-based study. MethodsWe measured HSV1 immunoglobulin (IgG) antibodies in serum collected between 2002 and 2005 from participants of the Rotterdam Study. We used linear regression to determine HSV1 in relation to change in cognitive performance during 2 consecutive examination rounds on average 6,5 years apart. Next, we determined the association of HSV1 with risk of dementia (until 2016) using a Cox regression model. We repeated analyses for Alzheimer’s disease. All models were adjusted for age, sex, cardiovascular risk factors, and apolipoprotein E genotype. Results Of 1,915 non-demented participants (mean age 71.3 years, 56.7% women), with an average follow-up time of 9.1 years, 244 participants developed dementia (of whom 203 Alzheimer’s disease). HSV1 seropositivity was associated with decline in global cognition (mean difference per standard deviation -0.16; 95% confidence interval (95%CI), -0.26; -0.07), as well as separate cognitive domains, namely memory, information processing, and executive function, but not motor function. Finally, HSV1 seropositivity was not associated with risk of dementia (adjusted hazard ratio, 1.18, 95%CI, 0.83; 1.68), similar for Alzheimer’s disease. DiscussionHSV1 is associated with cognitive decline but not with incident dementia in the general population. These data suggest HSV1 to be associated only with subtle cognitive disturbances but not with greater cognitive disorders that result in dementia.

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Herpes simplex virus 1 and the risk of dementia: a population-based study

Scientific Reports ◽

10.1038/s41598-021-87963-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Meghan J. Murphy ◽

Lana Fani ◽

M. Kamran Ikram ◽

Mohsen Ghanbari ◽

M. Arfan Ikram

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Cognitive Decline ◽

Population Based ◽

Herpes Simplex Virus 1 ◽

Population Based Study ◽

Global Cognition ◽

Simplex Virus

AbstractHerpes simplex virus 1 (HSV1) is a neuroinvasive virus capable of entering the brain which makes it a candidate pathogen for increasing risk of dementia. Previous studies are inconsistent in their findings regarding the link between HSV1 and dementia, therefore, we investigated how HSV1 relates to cognitive decline and dementia risk using data from a population-based study. We measured HSV1 immunoglobulin (IgG) antibodies in serum collected between 2002 and 2005 from participants of the Rotterdam Study. We used linear regression to determine HSV1 in relation to change in cognitive performance during 2 consecutive examination rounds on average 6.5 years apart. Next, we determined the association of HSV1 with risk of dementia (until 2016) using a Cox regression model. We repeated analyses for Alzheimer’s disease. All models were adjusted for age, sex, cardiovascular risk factors, and apolipoprotein E genotype. Of 1915 non-demented participants (mean age 71.3 years, 56.7% women), with an average follow-up time of 9.1 years, 244 participants developed dementia (of whom 203 Alzheimer’s disease). HSV1 seropositivity was associated with decline in global cognition (mean difference of HSV1 seropositive vs seronegative per standard deviation decrease in global cognition − 0.16; 95% confidence interval (95%CI), − 0.26; − 0.07), as well as separate cognitive domains, namely memory, information processing, and executive function, but not motor function. Finally, HSV1 seropositivity was not associated with risk of dementia (adjusted hazard ratio 1.18, 95% CI 0.83; 1.68), similar for Alzheimer’s disease. HSV1 is associated with cognitive decline but not with incident dementia in the general population. These data suggest HSV1 to be associated only with subtle cognitive disturbances but not with greater cognitive disorders that result in dementia.

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Alzheimer’s disease-associated β-Amyloid does not protect against Herpes Simplex Virus 1 infection in the mouse brain

Journal of Biological Chemistry ◽

10.1016/j.jbc.2021.100845 ◽

2021 ◽

pp. 100845

Author(s):

Olga Bocharova ◽

Narayan P. Pandit ◽

Kara Molesworth ◽

Aidan Fisher ◽

Olga Mychko ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Mouse Brain ◽

Herpes Simplex Virus 1 ◽

Β Amyloid ◽

Simplex Virus

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Herpes simplex virus, early neuroimaging markers and incidence of Alzheimer’s disease

Translational Psychiatry ◽

10.1038/s41398-021-01532-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Morgane Linard ◽

Marion Baillet ◽

Luc Letenneur ◽

Isabelle Garrigue ◽

Gwenaëlle Catheline ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Diffusion Tensor ◽

Hippocampal Volume ◽

Potential Interaction ◽

Increased Risk ◽

Simplex Virus ◽

Igg Level

AbstractWhile 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.

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