In surprising twist, some Alzheimer’s plaques may be protective, not destructive
April 16, 2021
NOMIS researcher Greg Lemke and colleagues at the Salk Institute have found that the brain’s immune cells form some plaques as a defense in Alzheimer’s disease, suggesting a new therapeutic direction.
LA JOLLA—One of the characteristic hallmarks of Alzheimer’s disease (AD) is the buildup of amyloid-beta plaques in the brain. Most therapies designed to treat AD target these plaques, but they’ve largely failed in clinical trials. New research by Salk scientists upends conventional views of the origin of one prevalent type of plaque, indicating a reason why treatments have been unsuccessful.
The traditional view holds that the brain’s trash-clearing immune cells, called microglia, inhibit the growth of plaques by “eating” them. The Salk scientists show instead that microglia promote the formation of dense-core plaques, and that this action sweeps wispy plaque material away from neurons, where it causes cell death. The research, which was published in Nature Immunology on April 15, 2021, suggests that dense-core plaques play a protective role, so treatments to destroy them may do more harm than good.
“We show that dense-core plaques don’t form spontaneously. We believe they’re built by microglia as a defense mechanism, so they may be best left alone,” says Greg Lemke, a professor in Salk’s Molecular Neurobiology Laboratory. “There are various efforts to get the FDA to approve antibodies whose main clinical effect is reducing dense-core plaque formation, but we make the argument that breaking up the plaque may be doing more damage.”
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Françoise Gilot-Salk Chair and professor in the Molecular Neurobiology Laboratory
Salk Institute for Biological Studies
NOMIS Center for Immunobiology and Microbial Pathogenesis