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Comment by dbcurtis | Hacker News Reader

> Alzheimer’s is driven by the buildup of toxic proteins called amyloid-beta.

Isn't the current thinking that amyloid-beta buildup is a marker, not a cause? The therapy may be working here, but it isn't clear whether clearing amyloid-beta proteins is the mechanism or an outcome.

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Yes. And to anyone paying attention, this has been current since about 2010.

I remember reading about this then and I am no where near the biomedical field.

I almost couldn't believe we are still talking about the same causes of alzheimers 16 years later.

From what I read your statement is accurate. From speaking to people who are going through the new infusions Leqembi and Kisunla get rid of amyloid plaque doesn't mean the decline stops, and if the disease was driven by it then it would stop.

Also, studies show some slowing using these new drugs, but the disease still progresses. Therefore, the plaque is most likely a symptom. It could be the driver in some of the cases though, I think in genetic PSEN1 alzheimer's. I've read a paper discussing issue with the body not removing it and allowing to build up.

I read it somewhere that amyloid plaques were actually defensive mechanism of the body to counter the damage to brain from disease, so removing the plagues makes things worse for patients

https://www.salk.edu/news-release/in-surprising-twist-some-a...

My wife’s family has PSEN1-mutation EAD (my wife didn’t inherit it). In that particular case it does seem that the mutated genes relate directly to Amyloid production and clearing, and there are ongoing clinical trials for the use of the new monoclonal antibody drugs in treating it. Two of my family members are in a trial for Remternetug, specifically. There is hope that in that specific case where 1. Amyloid buildup may actually be the cause and 2. you start treating it early, years before symptoms start, disease onset may be significantly delayed. There’s no way to know right now except to try it of course.

Are you family members experiencing any symptoms of the disease?

I guess if my mother has the gene I will test for PSEN1 at some point, but I am worried about the side effects of the meds. Hope things go well for your family.

My father in law passed away from it about a year and a half ago at age 64. Two of his kids have tested positive for the mutation. They don’t have symptoms yet (they’re in their 20s and 30s).

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