NATURE: The amyloid hypothesis on trial

Description

Although HSV has been found in the brains of people with and without Alzheimer’s disease, a study published in 1997 by Ruth Itzhaki, a neuroscientist at the University of Manchester, UK, suggests that the combination of HSV infection and the APOE ε4 gene variant confers a strong risk of developing the condition⁸. This implies that APOE could affect a person’s risk of Alzheimer’s disease by influencing their vulnerability to microorganisms, Itzhaki says. A decade later, having struggled to obtain funding to study this further, Itzhaki showed that infecting human cells or mice with HSV increased the level of amyloid-β⁹. “We had awful problems getting that published,” she says. “It’s been a series of battles.” In 2016, she and several colleagues published an editorial⁷ in the Journal of Alzheimer’s Disease, asserting that the role of microorganisms in Alzheimer’s disease had been neglected and calling for more research, including trials of antimicrobial agents. The article posited that certain microorganisms, when allowed to reside in the brain by an aged immune system, damage the organ both directly and indirectly through processes involving amyloid-β.