A new study in mice has shown that formation of brain protein plaques may be the first step towards Alzheimer's disease, and it can happen within a single day.
In the study, the researchers found that the plaques characteristic of Alzheimer's disease can form extraordinarily fast, and seem to be the starting point of further degeneration in the brain.
AdvertisementThat findings help to settle a long-standing debate about whether such plaques are a primary cause or a symptom of Alzheimer's, and may lead to new targets for Alzheimer's treatment.
Dennis Selkoe of Brigham and Women's Hospital in Boston, Massachusetts, who has worked in the past with the research team involved, said that the chicken-and-egg question about which comes first, protein plaques or damaged brain cells, has been 'argued about for decades.'
The debate has revolved around the clumps of a protein called amyloid-â that accumulate in the brains of patients with Alzheimer's disease. These protein plaques are surrounded by abnormal neurons and immune cells called microglia.
Selkoe said that it wasn't clear whether the plaques recruited microglia, or if the microglia caused the plaques.
To find out, Bradley Hyman of Harvard Medical School in Boston, Massachusetts and his colleagues used mice engineered with mutation that cause amyloid plaque formation and neural disease.
The researchers monitored plaque development over time in live mice and found that plaques can arise within a single day, much faster than expected.
"The plaques appeared very, very fast. People thought that it would take a matter of weeks or months," Nature quoted Eliezer Masliah of the University of California, San Diego, who was not involved in the study, as saying.
A few days after plaques' formation, microglia started to cluster around them. And after two weeks, projections from neighbouring neurons became progressively deformed.
Masliah thinks that the plaques may exude amyloid fragments that can travel a short distance in the brain and damage neurons.
Selkoe said that the timing of events strongly suggests that the amyloid plaques cause microglia accumulation, and not the other way around.
Hyman, in fact, hypothesizes that rather than seeding amyloid plaques, the microglia could instead restrain their growth.
"Once a plaque formed, it didn't change in size. This suggests that there is an active process that's limiting the growth," he said.
The researchers have warned that work done in mouse models may not directly apply to humans.
However, Masliah said that if amyloid plaques behave similarly in humans, their rapid growth could have implications for developing treatments.
The study is published in Nature.