Could Alzheimer's Spread Like Infection Throughout the Brain?
WEDNESDAY, May 1, 2019 (HealthDay News) -- With findings that might alter the path of Alzheimer's research, scientists say misfolded forms of two proteins appear to spread through patients' brains similar to an infection.
The findings suggest that Alzheimer's is a "double-prion" disorder. This discovery could help lead to new treatments that focus directly on prions, according to researchers from the University of California, San Francisco.
A prion is a misshapen protein that can force other copies of that protein into the same misfolded shape and spread in the brain. It's best known for its role in bovine spongiform encephalopathy -- "mad cow" disease -- and Creutzfeldt-Jakob disease (CJD), a degenerative brain disorder.
In the new research, the university team analyzed the brains of 75 Alzheimer's patients after death and found self-propagating prion forms of the proteins amyloid beta and tau. Higher amounts of these prions were associated with early-onset Alzheimer's and younger age at death.
Alzheimer's patients have amyloid plaques and tau tangles in the brain, but efforts to treat the disease by clearing out these inactive proteins have failed.
These new findings suggest that active amyloid beta and tau prions could drive Alzheimer's and offer targets for effective treatment, according to the researchers.
"I believe this shows beyond a shadow of a doubt that amyloid beta and tau are both prions, and that Alzheimer's disease is a double-prion disorder in which these two rogue proteins together destroy the brain," said study senior author Dr. Stanley Prusiner, director of the UCSF Institute for Neurodegenerative Diseases. Prusiner won a Nobel Prize in 1997 for discovering that prions were responsible for mad cow disease and CJD.
Prion levels also appear linked to patient longevity, he noted.
"We need a sea change in Alzheimer's disease research, and that is what this paper does. This paper might catalyze a major change in AD research," Prusiner said in a university news release.
For this study, the researchers used recently developed laboratory tests to rapidly measure prions in human tissue samples. They can reveal infectious prion levels in just days.
These tests "are a game-changer," said study co-author William DeGrado, a UCSF professor of pharmaceutical chemistry.
In order to develop effective therapies and diagnostics, scientists must target the active prion forms, rather than the large amount of protein in plaques and tangles, DeGrado said.
The researchers hope that measuring the prion forms of amyloid beta and tau might lead to the development of drugs that either prevent them from forming or spreading, or help remove them before they cause damage.
The study was published May 1 in the journal Science Translational Medicine.
The U.S. National Institute of Neurological Disorders and Stroke has more on Alzheimer's disease.
SOURCE: University of California, San Francisco, news release, May 1, 2019