Basic Science and Pathogenesis.

Area of Science:

• Neuroscience
• Genetics
• Infectious Diseases

Background:

• Herpes Simplex Virus Type 1 (HSV-1) is increasingly implicated in Alzheimer's Disease (AD) pathogenesis.
• This study investigates the association between HSV-1 and AD using neuroimaging and genomic data.

Purpose of the Study:

• To examine the relationship between HSV-1 presence and brain structural alterations in AD.
• To determine if HSV-1 exacerbates cerebral atrophy in AD and mild cognitive impairment (MCI).

Main Methods:

• Utilized whole-genome sequencing and MRI data from Framingham Heart Study (FHS) and Alzheimer's Disease Sequencing Project (ADSP) cohorts.
• Assessed HSV-1 DNA presence and correlated it with brain volume and cortical thickness using linear regression models.
• Conducted meta-analysis to combine results from FHS and ADSP cohorts.

Main Results:

• HSV-1 DNA presence was associated with significant differences in 19 brain regions, affecting volume and thickness.
• A significant interaction between HSV-1 and AD/MCI was observed in six brain regions.
• HSV-1 DNA correlated with increased surface holes and accelerated thinning in specific brain areas, notably the accumbens and temporal regions.

Conclusions:

• Findings suggest HSV-1 may exacerbate cerebral atrophy associated with Alzheimer's Disease.
• Further research is necessary to confirm these associations and understand the underlying biological mechanisms.