I will never understand your circular reasoning that mRNA expression will not be accepted as an AD (or a more general CNS) efficacy biomarker because there is no precedent for it being such a biomarker. Of course, the logic of that that argument demands that mRNA expression will never be an FDA-accepted biomarker since it will never have been previously approved. And it wouldn't matter if it actually correlates to improved clinical results as I, at least, expect it will. The logic extends just as strongly to any novel biomarker for CNS diseases.
On the other hand, the FDA has approved the statistically unproven amyloid biomarker for Aduhelm (although the rest of the medical market isn't going along) and *this* discreditable avenue seems to be your basis for hope for 2-73.
I suppose I should just look at this ridiculous construct of an argument as a breathtaking example of cynicism, or perhaps a satire, because it certainly treats the scientific method, and FDA scientists, with contempt.
It also ignores the fact that a safe and clinically meaningful efficacious CNS drug can and almost surely will receive approval, biomarker or not.