A new research study from Rudolph Tanzi, PhD, and Robert Moir, PhD, researchers in the Department of Neurology at Massachusetts General Hospital, has uncovered a Jekyll and Hyde role for a naturally occurring protein in the brain most commonly associated with Alzheimer’s disease (AD).
In conjunction with new findings from another research team at Icahn School of Medicine at Mount Sinai, their results add to mounting evidence to suggest that viral and other infections may play an important role in the cause and progression of AD. The findings also point to a potential new treatment for the devastating neurological condition.
The good and bad sides of amyloid beta
Everyone has amyloid-β (Aβ) protein in their brain. When Aβ clumps together to form plaques, it collects between neurons and disrupts cell function, ultimately leading to the symptoms of AD.
However, Aβ isn’t always the bad guy. In previous recent research studies, Tanzi and Moir discovered that Aβ on its own acts as an antimicrobial that protects the brain against fungal and bacterial infections and viruses, cumulatively known as pathogens.
Herpes virus risk
Of all the human pathogens, the herpes simplex virus 1 (HSV1) — one of multiple herpes strains able to infect humans — is the virus most frequently linked to AD. A recent study following 33,000 patients over 16 years found that HSV1 infection increases AD risk 2.5 fold.
Why is herpes a concern for aging populations? It’s estimated that nearly everyone carries herpes in their system, though it can often lay dormant with no symptoms. As immunity and blood-brain barrier integrity decline with age, herpes is better able to travel from the peripheral nervous system to the central nervous system and infect the brain.
If the virus begins to replicate in the brain, Aβ springs into action by clumping around the virus particles, trapping and neutralizing them within insoluble plaques.
The downside of this immune response is that high plaque levels drives neuroinflammation, leading to widespread neuron death and, eventually, dementia. Thus, increased herpes pathogen activity in brain over time can accelerate the progression of AD by ramping up the generation of plaques.
Tanzi and Moir believe that in AD, this normally protective antimicrobial pathway is continually activated, either by HSV1, other brain microbes or possibly even as a response to an incorrectly perceived infection.
Studying the brain’s protective system
To better understand this protective system, Tanzi, Moir and their team studied herpes in 3D cultures of human neurons and transgenic AD mice that express human Aβ.
They found that in the AD mice and 3D cultures of human brain cells, Aβ does indeed protect against herpes infection by binding and entrapping the viral particles. Most pertinent to AD, this protective response against viral infection also seeded and accelerated the clumping and deposition of Aβ as harmful plaques. Complementary new findings from a research team based at Icahn School of Medicine at Mount Sinai confirmed that herpes viruses are more active in AD brain.
Tanzi and Moir’s findings, together with those of the Mount Sinai team, provide evidence to suggest that herpes infection may directly promote Aβ build up and accelerate the progression of AD.
Moreover, these two studies raise the possibility that anti-herpes medications may help slow the onset of dementia for patients with herpes brain infections.
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