Scientists have long been racking their brains for ways to treat Alzheimer’s disease, the most common type of dementia.
Turns out that the answer may lie within our own brains. Researchers from Northwestern University suggest that enhancing the brain’s immune cells may better equip them to clear out harmful clumps of the toxic protein amyloid beta, a hallmark of Alzheimer’s.
“Our study is highly novel because we had the rare opportunity to analyze one of the largest post-mortem brain cohorts of Alzheimer’s patients treated with amyloid-targeting drugs — similar to those now approved by the FDA for Alzheimer’s disease,” lead author Lynn van Olst said.
The researchers examined 13 brains vaccinated with amyloid beta, six brains with Alzheimer’s that had not received that treatment and six disease-free brains.
Amyloid beta is a small protein fragment that forms plaque-like deposits when it accumulates abnormally in the brain. Vaccination is supposed to trigger the immune system to produce antibodies to remove the plaques.
But clinical trials of amyloid beta vaccines for Alzheimer’s have repeatedly failed. Dangerous brain swelling has been a major side effect.
The challenge for vaccine developers is to create an immune response that can combat amyloid beta without attacking healthy cells.
The US Food and Drug Administration has approved a few antibody treatments for Alzheimer’s that target amyloid beta. They are given as intravenous infusions.
“These drugs stimulate the immune cells of the brain to remove amyloid beta, but we believe that the data in our publication can be utilized to make these drugs work even better,” said corresponding study author David Gate, a Northwestern assistant professor of neurology.
The Northwestern team found that when these types of treatments work, the brain’s immune cells — known as microglia — clear plaques and help restore a healthier brain environment.
Of the 13 vaccinated brains, seven had high levels of plaque clearance. The other six had limited clearance.
“Our study is the first to identify the mechanisms in microglia, the brain’s immune cells, that help limit the spread of amyloid in certain brain regions following treatment with amyloid-targeting drugs,” said Gate, director of the Abrams Research Center on Neurogenomics.
Gate’s team found that only some microglia are effective at removing plaques. Factors for success include brain region, type of immunization and gene activity.
The good news is that microglia aren’t always focused on amyloid removal.
“They can remove the amyloid and then go back to being good and appear to actually help the brain heal,” Gate said.
The bad news is that directly targeting microglia is still a challenge.
“If we can define the mechanisms that are associated with clearance of the pathology, and we can find the genetic makeup of immune cells that are associated with people that are really responding well to the drug, then maybe one day we can circumvent the whole drug process and just target these specific cells,” Gate said.
Gate’s conclusions were published Thursday in Nature Medicine.
He told The Post that the team is acquiring brain tissues of patients who received the new anti-amyloid antibodies to explore their efficacy and is investigating how to apply these findings to other neurodegenerative diseases, such as Parkinson’s disease and ALS.
Alzheimer’s affects an estimated 7 million Americans while nearly 1 million Americans are afflicted with Parkinson’s. Less than 30,000 Americans are believed to have ALS.
