Ok folks, let's put a bit of perspective on the announcement from this morning:
1. No change in ADAS-Cog is not surprising, given the short duration of the trial. Even if amyloid is removed, improvement in cognition will arise thru repair of damaged cells which, in a stable cell turnover environment such as the brain, will take many months.
2. I'm wary of the emphasis given to improvement in other cognitive subscales. Remember the Clioquinol trial, where post-hoc analysis of data was used to demonstrate statistically significant cognitive changes "in a subgroup of patients?" The improvement in executive function cited smacks very much of this post-hoc analysis, or data-trawling, in an effort to find something positive to say on the cognitive front.
3. (The big one!) CSF beta-amyloid drops as dementia severity increases in Alzheimer's. This is because soluble amyloid (that which is measurable in CSF) is in equilibrium with insoluble plaque amyloid. As the disease progresses, more of the amyloid pool is deposited in the solid form, causing a drop in the CSF levels. Thus, to me, it seems that the DROP in CSF beta amyloid is the OPPOSITE result to that expected (a rise, as plaque amyloid is dissolved).
It will be very interesting to see how the company spins this.
I've sold the majority of my holding, but am retaining a small amount to see how this pans out.
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