There are actually three amyloid antibodies that have shown some success: aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab. I think the FDA approval of aducanumab was absolutely the right decision, though it’s far from a miracle drug.
I spent about six months of my life buried in the Alzheimer literature. There’s a mountain of evidence for this hypothesis. Take a look at my previous comments if you’re curious.
[T]his error strikes me as … emblematic of a certain common failure mode within the rationalist community (of which I count myself a part). This common failure mode is to over-value our own intelligence and under-value institutional knowledge (whether from the scientific community or the Amazon marketplace), and thus not feel the need to tread carefully when the two come into conflict.
In that comment and the resulting thread, we discuss the implications of that with respect to the rationalist community’s understanding of Alzheimer’s... (read more)
Update today: Biogen/Eisai have reported results from Lecanemab’s phase 3 trial: a slowing of cognitive decline by 27% with a p-value of 0.00005 on the primary endpoint. All other secondary endpoints, including cognitive ones, passed with p-values under 0.01.
I'd also recommend this article, including the discussion in the comments by researchers in the field.
A crucial distinction I'd emphasize which is almost always lost in popular discussions is that between the toxic amyloid oligomer hypothesis, that aggregates of amyloid beta are the main direct cause of neurodegeneration; and the ATN hypothesis I described in this thread, that amyloid pathology causes tau pathology and tau pathology causes neurodegeneration.
The former is mainly what this research concerns and has been largely discredited in my op... (read more)
In brief, the main reason I don't think the argument works that autosomal-dominant Alzheimer's has a different etiology than sporadic Alzheimer's is that they look, in so many respects, like essentially the same disease, with the same sequence of biomarkers and clinical symptoms:
Amyloid pathology starts in the default mode network, and gradually spreads throughout the brain over 15-20 years.
It eventually reaches the medial temporal region, where Primary Age-Related Tauopathy is lying in wait.
At this point, tau pathology, a prion-like pathology which in Alz
A distinction is made in the literature between preclinical Alzheimer's (the presence of neuropathology such as amyloid-β, without clinically detectable cognitive symptoms) and clinical Alzheimer's (a particular cluster of cognitive symptoms along with the neuropathologies of Alzheimer's). It's currently believed that Alzheimer's has a 15-20 year preclinical phase, the duration of which, however, can vary based on genetic and other factors.
In the case of the mutations I mentioned (which are early-onset causing), clinically-detectable cognitive decline typi... (read more)
I apologize if this is piling on, but I would like to note that this error strikes me as very similar to another one made by the same author in this comment, and which I believe is emblematic of a certain common failure mode within the rationalist community (of which I count myself a part). This common failure mode is to over-value our own intelligence and under-value institutional knowledge (whether from the scientific community or the Amazon marketplace), and thus not feel the need to tread carefully when the two come into conflict.
There are actually three amyloid antibodies that have shown some success: aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab. I think the FDA approval of aducanumab was absolutely the right decision, though it’s far from a miracle drug.
I spent about six months of my life buried in the Alzheimer literature. There’s a mountain of evidence for this hypothesis. Take a look at my previous comments if you’re curious.