Anti-Alzheimer's antibodies clean out brain plaques in mice
Researchers from the Washington University School of Medicine have tested a new weapon in the fight against Alzheimer's. In mice tests, the team has demonstrated an antibody that can clear away the disease's characteristic build-up of proteins in the brain, which may lead to an early-stage treatment to prevent symptoms from occurring.
Fragments of a protein known as beta amyloid are a waste product of the brain's everyday processes and normally this clutter is regularly cleared away. But over time these fragments can clump together and harden into amyloid plaques, and their interference with neurons and brain function results in the loss of memory and perception we associate with Alzheimer's.
"Many people build up amyloid over many years, and the brain just can't get rid of it," says David Holtzman, senior author of the new study. "By removing plaques, if we start early enough, we may be able to stop the changes to the brain that result in forgetfulness, confusion and cognitive decline."
These plaques can start to build up in the brain years or even decades before the symptoms show, giving us plenty of time to detect it before it starts doing real damage. Past research has looked at blood tests, eye exams and sniff tests for early diagnosis, which could give treatments currently under development a greater chance of success down the track.
One such avenue of treatment may be antibodies, which have in the past shown promise as valuable candidates for breaking down the plaques of neurodegenerative diseases. Unfortunately, this can come with the side effect of triggering a strong immune response, leading to swelling and inflammation in the brain.
To overcome that problem, the Washington study targeted a protein named APOE, which is bundled up in small amounts in the amyloid plaques. The researchers experimented with several antibodies that bind to APOE, to test the idea that clearing away these proteins might also destroy the amyloid in the process.
"The anti-amyloid antibodies are going to be binding to most of the molecules that are in the plaque, but the anti-APOE antibody would target just a very small component of the plaque," says Holtzman. "This means we may find less immune activation, and we might not see the unwelcome side effects."
So the team engineered mice that had a human APOE gene, and were predisposed to develop amyloid plaques. Once a week for six weeks, the team gave these mice injections of either APOE-targeting antibodies or a placebo, and then checked their brain plaque levels at the end of the treatment.
One antibody, known as HAE-4, showed particular promise. It managed to halve the amount of amyloid plaques in the mice and was selective enough to only target APOE in the brain, not in the blood where it could trigger side effects.
"It turns out that the APOE in the plaques has a different structure than the form of APOE found in the blood," says Holtzman. "The HAE-4 antibody recognized only the form found attached to the plaques in the brain."
Next up, the researchers plan to explore similar antibodies and ultimately prepare the treatment for eventual human trials.
The research was published in The Journal of Clinical Investigation.
Source: Washington University