Herpesvirus-induced neuroinflammation in the peripheral nervous system (PNS) as a ‘distant’ trigger of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting

26 million people worldwide. To date, there is no cure and current

therapies are not effective in delaying progression. Thus, there is an

urgent need to change the way of looking at the disease and to

rethink possible therapies. Herpes simplex virus type 1 (HSV1) has

recently received growing attention for its role in AD. HSV1 infects

the mouth and invades peripheral sensory nerves. The virus remains

inactive in sensory neurons but when a person is stressed, it can

reactivate and return to the mouth, resulting in cold sores.

Occasionally, the virus spreads from peripheral neurons to the brain

after reactivation. The objective of HERPINAD is to provide a clear

understanding of how common HSV1 infection plays a role in the

initiation of AD. The hypothesis is that HSV1 infection of peripheral

neurons causes inflammation which is relayed to neurons in the

brain, resulting in long-term inflammation and neurodegeneration.

This neuroinflammation represents the driving force of AD pathology,

starting very early in the course of the disease. The paradigm shift

will focus on the peripheral nervous system and will be away from the

current thinking that the brain is directly infected by HSV1. This work

will be performed using our new mouse model to study herpesvirusinduced

neuroinflammation. Our findings will be of key importance for

the design of new therapies that may prevent AD to the current and

future generations.