Alzheimer's Imaging Consortium.

Area of Science:

• Neuroscience
• Virology
• Genetics

Background:

• Herpes simplex virus type 1 (HSV-1) infection is implicated in Alzheimer's Disease (AD) pathogenesis.
• Latent herpes infections may influence amyloid and tau pathology, but the direct link to HSV-1 presence and protein deposition is unclear.

Purpose of the Study:

• To investigate the association between HSV-1 DNA quantity and brain amyloid-β and tau deposition in Alzheimer's Disease.
• To explore the relationship between HSV-1 presence and neurodegenerative markers.

Main Methods:

• Quantified HSV-1 DNA in whole-genome sequencing data from ADNI and Wisconsin Registry for Alzheimer's Prevention participants.
• Utilized amyloid-β and tau PET imaging data.
• Employed linear regression models to assess associations between HSV-1 DNA and tau/amyloid SUVRs, controlling for AD status, age, and gender.

Main Results:

• HSV-1 DNA was detected in 300 participants.
• No significant association was found between HSV-1 DNA and amyloid PET metrics.
• HSV-1 DNA showed a significant association with *decreased* tau levels in multiple brain regions, including the hippocampus, cerebral white matter, amygdala, CSF, and caudate.

Conclusions:

• HSV-1 infection may have a complex role, potentially offering protection against tau accumulation in various brain regions.
• The findings suggest a potential reciprocal protective effect between tau and HSV-1.
• Further investigation is warranted to elucidate the mechanisms underlying the HSV-1 and tau interaction in neurodegeneration.