Read our COVID-19 research and news.

An Alzheimer's Plaque Provocateur

Scientists have learned that a protein produced in response to injury can accelerate the growth of abnormal protein deposits--called amyloid plaques--like those seen in the brains of Alzheimer's disease patients. The study was done in mice, but the team also found indications of higher levels of the protein, called transforming growth factor-beta1 (TGF-beta1), in tissue from people who had Alzheimer's. The findings, reported in tomorrow's issue of Nature, suggest that drugs designed to block the effects of TGF-beta1 might be able prevent the deposition of plaques associated with the disease.

What triggers the buildup of amyloid--a substance made up of protein fragments that can damage and kill brain cells--has been a long-standing mystery. Neuroscientist Lennart Mucke of the Gladstone Institute and the University of California, both in San Francisco, and his colleagues knew that TGF-beta1 increases the production of several compounds that might affect amyloid deposition. To test their idea, they developed mice genetically engineered to overproduce TGF-beta1 in their brains. As the mice aged, they developed brain amyloid deposits closely resembling those found in humans with Alzheimer's disease. No such deposits were found in normal mice.

By breeding these TGF-beta1 transgenic mice with mice that produce human amyloid proteins, the researchers found that TGF-beta1 also accelerated the formation of human amyloid deposits in the brains of these doubly transgenic mice. The researchers then analyzed brain tissue taken post-mortem from 15 patients with Alzheimer's, looking for the messenger RNA that produces TGF-beta1. The levels, they found, were three times higher than in seven people without the disease. Taken together, these results strongly suggest that TGF-beta1 can effectively initiate or accelerate the deposition of amyloid proteins in the brain, says Steven DeKosky, a neurologist at the University of Pittsburgh.

If researchers can develop a way to block excessive production of TGF-beta1, "it is potentially a fruitful way of preventing disease in people with early or preclinical Alzheimer's disease," he says. DeKosky notes that the findings might also have implications for treating people with brain hemorrhages and some stroke patients, because amyloid proteins may be involved with hemorrhages.