Chicago scientists make key finding that may improve Alzheimer’s drugs
by: Dina Bair, Katharin Czink
Posted: Mar 12, 2025 / 04:33 PM CDT
There has been progress. The latest Alzheimer’s drug appears to tackle the characteristic features of the disease in the brain. Now Chicago area scientists say they have identified the genes that drive the process and now want to make the drug even better.
Lynn van Olst left the Netherlands and brought her expertise to Chicago to study Alzheimer’s, particularly the role our own immune cells play in the mind-robbing disease.
“I’m a neuro-immunologist so my passion is looking at immune cells,” she said.
In her latest study, she looked at multiple brain samples from a failed clinical trial and one from a more recent patient.
“Then we also had one brain treated with one of the newer drugs that is on the market right now,” she said.
That new drug is called Lecanemab. It’s designed to clear away the amyloid beta plaques known to play a role in Alzheimer’s disease.
“We don’t want to advocate pro or con these treatments,” van Olst said. “What we want to do is understand how they work in the brain, which genes are involved, so we can improve them.”
There’s room for improvement.
With the help of a new tool that serves as a sort of GPS of the brain, the research team tracked where the plaques were removed and identified which genes were activated to clear the toxic substances.
The team studied one of the first brains available from a deceased subject who received the new anti-amyloid drug. Days after her last Lecanemab infusion, the patient appeared to be having a stroke, and doctors administered a common stroke treatment known as TPA.
“She came in with these stroke-like symptoms and they treated her for that,” van Olst said. “And the treatment that they give for her at that moment, we know right now doesn’t go well with the drug, but at that moment that information was not available.”
Lecanemab did in fact activate immune cells that then cleared the amyloid plaque from the patient’s brain.
“We believe that these immune cells at the blood vessels might have a key role in the side effects to these drugs,” Van Olst said. “And we are going to try to understand that better by looking into brains that experience these side effects.”
Genetic factors also play a role, specifically a variant known as APOE4. Another nuance is while the treatment did work to remove amyloid plaque from the brain, it did not appear to stop the spread of what’s called tau pathology – tau is a toxic substance that is closely linked to cognitive decline in Alzheimer’s disease.
“So we think that either this treatment is not specific enough or not early enough we don’t know which of the two it is,” she said. “We know what kind of genes are active right here. Our second question is what kind of genes are active right here and if we know that can we then make these drugs a little bit better and a little bit more specific.”
The team is not working with the drug’s maker – this is independent research using donated brain tissue. In their next study, the researchers plan to take a closer look at the cells and genes involved in attacking the blood vessels in people who have side effects following treatment.