What if Alzheimer's isn't just about the buildup of toxic proteins — but about the immune cells that were supposed to clean them up, and why they eventually stop doing their job?
Thank you for this article, Hussein! I keep thinking about how anti-amyloid antibodies might actually be exhausting already-compromised microglia in APOE4 carriers rather than rescuing them. The timing question feels underappreciated in the clinical conversation.
It is a good question. These treatments trigger microglia to phagocytose and clear abeta. Whether they induce a state of exhaustion is not known. However, tiggering this pathway in blood vessels with abeta provides an explanation for the side effect ARIA, where the blood vessel becomes inflamed with immune cells trying to clear amyloid.
Thank you for this article, Hussein! I keep thinking about how anti-amyloid antibodies might actually be exhausting already-compromised microglia in APOE4 carriers rather than rescuing them. The timing question feels underappreciated in the clinical conversation.
It is a good question. These treatments trigger microglia to phagocytose and clear abeta. Whether they induce a state of exhaustion is not known. However, tiggering this pathway in blood vessels with abeta provides an explanation for the side effect ARIA, where the blood vessel becomes inflamed with immune cells trying to clear amyloid.
Say more!!!