. Alzheimer's disease-linked mutations in presenilin-1 result in a drastic loss of activity in purified γ-secretase complexes. PLoS One. 2012;7(4):e35133. PubMed.


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  1. If it turns out that FAD mutations are generally loss of function, then the phenotype of haploinsufficiency would be the same as partial inhibition with γ-secretase inhibitors. Is this is why γ-secretase inhibitors failed in Phase 3? Maybe degrading APPβ CTF is a good thing?

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