For more than three decades, scientists have been struggling to stop Alzheimer’s disease, removing beta amyloid plates – sticky clusters of toxic protein that accumulate in the brain. Now, a new study of northwestern medicine indicates a very promising alternative: Strengthening brain immune cell cells to clean these plates more effectively.
The findings could reform the future of Alzheimer’s treatments, shifting the focus from simply removing the plates to exploit the natural defenses of the brain.
Previous Alzheimer’s vaccine attempts failed when the immune system response caused dangerous brain edema. Even today’s antibody treatments approved by the FDA remain controversial, providing only average benefits with possible side effects and high price points.
I think everyone agrees that, although these medicines are becoming more and more effective, they ultimately do not cure patients with Alzheimer’s disease. These drugs stimulate the brain’s immune cells to remove amyloid beta, but we believe that the data in our publication can be used to make these drugs work even better. “
David Gate, corresponding writer, Assistant Professor of Neurology at Northwestern University FEINBERG School of Medicine and Director of the Abrams Research Center for Neurogenomics
The document will be published on March 6 in nature medicine.
The study is the first to use a cutting -edge technique called a spatial transcriptional in human clinical brain test with Alzheimer’s disease. The technique allows scientists to identify the specific spatial position of gene activity in a sample of tissue.
Analyzing brain tissue donation by deceased people with Alzheimer’s disease who received amyloid -bite immunization and compared to those who did not do so, scientists found that when these treatments work, the brain immune cells (who are also called the brain) brain.
But not all microtics are created equal. Some are quite effective in removing the plates, while others are struggling, the study found. Also, the microtogy in brain treated adopt separate conditions depending on the brain area and the type of immunization. Finally, some genes, such as Trem2 and APOEThey are more active in microgly in response to treatment, helping these cells remove beta amyloid plates, according to findings.
“A long -term question in the field of Alzheimer’s therapeutic disease is whether these immune cells homogeneous in removal of amyloid. Is it always in this way of removing amyloid?” Said the gate. “The answer we found is no. They can remove the amyloid and then return to being good and really seem to help the brain heal.”
Stoping Alzheimer’s “domino” to fall
The amyloid waterfall case, the prevailing theory of Alzheimer’s disease, can be compared to a series of domino. If the amyloid plates can be cleaned by the brain before activating the formation of the TAU pathology – the main guide of cognitive decline to Alzheimer’s patients – the waterfall stops before it begins, preventing further damage.
“The idea is that in people who already have Alzheimer’s disease, yes, you may probably remove the amyloid, but if the spread of Tau has been put on motion, you are struggling in an uphill battle,” Gate said. “But perhaps, if you face people so early that they still don’t have a tau’s pathology. You can stop the domino result.
“If we can determine the mechanisms associated with the purification of the pathology and we can find the genetic makeup of immune cells associated with people who really respond well to the drug, then maybe one day we can bypass the whole pharmaceutical process and target them.
Currently, there is no way to target these immune system cells, Gate said, but cell targeting methods are improved annually.
How was the study conducted
The study included six control brains that had no neurological disease. Six brains with Alzheimer’s disease that had not been treated with any immunization drug. and 13 brains that were vaccinated with beta amyloid. Of these 13, the seven had high levels of amyloid-plow clearing in the brain, while the other six had limited quantities of liquidation.
Scientists then compared the immune cells to the brains between these two groups.
“Our study is extremely new because we had the rare opportunity to analyze one of the largest post-mortem brain groups of Alzheimer’s patients who were treated with amyloid target drugs-now approved by the FDA for Alzheimer’s disease,” said Chief
“This has allowed us to explore the brain mechanisms that determine why some people respond well to these treatments and clearly the toxic amyloid veto, while others do not.
Study funding is provided by National Institutes of Health Institutes of Aging R01 Grant AG078713, Brightfocus Foundation A2023003s, Alzheimer’s Association Nederland Early Career Grant.03-2023-08.
Source:
Magazine report:
Van Olst, L., et al. (2025). Micro mechanisms lead to amyloid-B purification to immunized patients with Alzheimer’s disease. Natural medicine. Doi.org/10.1038/S41591-025-03574-1.
