"Crosstalk" Between Genes Promotes Brain Inflammation in Alzheimer's Disease
In This Article
- The gene CD33 has been associated with neuroinflammation in Alzheimer's disease (AD) as it turns microglia cells into neuron killers when highly expressed
- In a recent study, Rudolph Tanzi, PhD, Ana Griciuc, PhD, and colleagues at Massachusetts General Hospital studied relationships between CD33 and TREM2 genes in mice specifically bred to have brain changes and behavior consistent with AD
- The team found that AD mice performed better on learning and memory tests when CD33 was silenced, while behavior did not change when only TREM2 was silenced or when both genes were silenced
- The study establishes these two genes as promising drug targets for preventing neuroinflammation and the development of AD
A new study at Massachusetts General Hospital reveals more information about how to prevent neuroinflammation, a response to the buildup of amyloid plaques that promote Alzheimer's disease (AD).
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Rudolph E. Tanzi, PhD, director of the Genetics and Aging Research Unit at Mass General, Ana Griciuc, PhD, neuroscientist, and colleagues sought to learn more about "crosstalk" between genes and how genetic relationships can contribute to the onset of AD.
Tanzi's lab previously discovered the first gene associated with neuroinflammation in AD, known as CD33. In 2013, Dr. Tanzi and colleagues reported that CD33 influences the activity of microglia, sparking neuroinflammation by turning microglia from housekeepers to neuron killers.
Now Dr. Tanzi, Dr. Griciuc and colleagues have identified another gene—TREM2—which balances the influence of CD33 on microglia by shutting down microglia's capacity to promote neuroinflammation. To study the relationship between the two genes and what occurs when one or both genes are silenced, the team studied laboratory mice specifically bred to have brain changes and behavior consistent with AD.
In AD mice that had their CD33 genes turned off, levels of amyloid plaque were reduced, and mice performed better on tests of learning and memory. When both CD33 and TREM2 were silenced, however, the mice did not show any brain or behavior benefits. Mice with only TREM2 silenced showed the same outcome. Dr. Tanzi says this tells us that TREM2 is working downstream of CD33 to control neuroinflammation.
The results of the study indicate that CD33 and TREM2 are very promising drug targets for reducing the brain nerve cell death that is caused by neuroinflammation.
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