In This Article
- From the 1980s, scientists have understood that peptide beta-amyloid is a toxic byproduct, and that deposits of amyloid plaque in the brain was a hallmark of Alzheimer's disease
- However, Robert Moir, PhD, believed beta-amyloid formed plaques in the brain as an immune response to microbes and specifically, herpes simplex virus 1 (HSV-1), which is more common with age
- Because his hypothesis was unconventional, NIH often denied his requests for funding in support of conventional projects that only targeted beta-amyloid, but were ineffective at stymying Alzheimer's
- His findings showed that herpes might stimulate continued activation of the beta-amyloid immune response, suggesting that inflammation and not beta-amyloid destroys synapses and neurons
For decades, scientists have understood that peptide beta-amyloid is a toxic byproduct. Deposits of amyloid plaque in the brain is a hallmark of Alzheimer's disease. They believed that eliminating the plaques would reverse or slow the disease, which has not worked.
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For years, this unconventional belief failed to produce effective drugs and created barriers for scientists like Robert Moir, PhD, a neurobiologist at Massachusetts General Hospital, to receive support for innovative ideas and new findings.
Dr. Moir noticed that all vertebrates made beta-amyloid and that in almost all species, the beta-amyloid was identical to humans'. He believes that this peptide evolved about 400 million years ago, which suggests that beta-amyloid must have a significant physiological role.
Encouraged by Rudolph Tanzi, PhD, director of the Genetic and Aging Research Unit at Mass General, in 2009, after infecting microbes with beta-amyloid in test tubes for three years, Dr. Moir and his colleagues found that beta-amyloid plaques trapped and destroyed microbes.
He next moved to experimenting with Alzheimer's brain tissues. Using 32 tissues, taken 12 to 24 hours after death, and 13 from healthy brains, Dr. Moir injected them with a fungus called candida. The fungus grew less in the Alzheimer's tissues than in healthy tissues, but when Dr. Moir added antibodies that stunted beta-amyloid function, candida growth increased in the Alzheimer's tissues.
Their finding was published in March 2010, earning him a five-year NIH grant to conduct studies on mice, which were genetically engineered to form human beta-amyloid plaques in five months. After injecting salmonella into the brains of these mice, amyloid plaques formed. This work was published in Science Translational Medicine, and named one of the top neurology advances for 2016.
Turning to a recent grant from the Boston-based Cure Alzheimer's Fund, Dr. Moir tested a hypothesis that herpes simplex virus 1 (HSV-1) could reach the brain and promote amyloid plaques. After he injected herpes viruses into the Alzheimer's-in-a-dish created by Dr. Tanzi and his colleagues, amyloid plaques formed in synapses, caused tau tangles to form inside and kill neurons and sparked inflammation, an immune response.
His finding revealed that herpes in the brain, which is more common with age, might continuously stimulate the amyloid immune response, inflammation, which destroys synapses and neurons. Because amyloid protects against viruses, new treatments will target inflammation, which can destroy 10 neurons for every one that destroyed by beta-amyloid and tau tangles, according to Dr. Tanzi.
Learn more about the Mass General Institute for Neurodegenerative Disease
Learn more about the Tanzi Lab