Public Health

Area of Science:

• Neuroscience
• Virology
• Gerontology

Background:

• Previous research suggests a link between herpes simplex virus 1 (HSV-1) and Alzheimer's disease (AD) pathophysiology.
• Neuroimaging studies investigating this association are limited.
• Susceptibility factors may modulate the impact of HSV-1 on AD-related brain changes.

Purpose of the Study:

• To investigate the association between HSV-1 infection and neuroimaging markers of AD.
• To evaluate how factors like cytomegalovirus (CMV) co-infection, APOE4 genotype, and age influence this relationship.

Main Methods:

• Analysis of serological and MRI data from a UK Biobank subsample (n=901).
• Linear regressions assessed associations between HSV-1 seropositivity and grey matter (GM) volumes in AD-vulnerable brain regions.
• Interactions with CMV, APOE4, and age were tested, with stratifications performed to assess modulating effects.

Main Results:

• HSV-1 infection alone showed no significant association with GM volumes in the studied brain areas.
• HSV-1 infection was linked to reduced parahippocampal volume only in participants without CMV infection (p=0.03).
• Among APOE4 carriers aged 65+, CMV infection (alone or with HSV-1) was associated with lower amygdala volume (p=0.04) and trends towards reduced GM in other regions.

Conclusions:

• The relationship between viral infections and AD neuroimaging markers is complex.
• Viral co-infections (e.g., HSV-1 and CMV), age, and APOE4 genotype are crucial susceptibility factors.
• These factors are important for understanding the role of infections in AD pathogenesis.