. Presenilins are not required for A beta 42 production in the early secretory pathway. Nat Neurosci. 2002 Sep;5(9):849-55. PubMed.


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  1. Adding this type of fuel to a scientific debate is exciting. In the light of what is known (and not known) of APP and PS1, i.e. their normal function and their contribution to AD, this paper cannot but raise more questions. Too many cooks can ruin the dish, and too many dogma's can ruin a research-field. On the other hand, there are never enough good experiments and this paper provides some. Still, it would have been wise to diagnose a PS1 knock-out by genotyping and not only by looking at a E15 mouse embryo. Also, overexpression of APP by SFV can be too much of a good thing. Despite these technical points, one cannot but wonder about the identity of the 3rd gamma-secretase ...

  2. Previous studies by Checler suggested that A β could be produced by cells lacking PS1 and PS2. This current paper provides support for this surprising result, and identifies the specific compartment in which the A β species is produced, which could help to identify how A β is produced in absence of PS.

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  1. Semagacestat, a Pseudo γ-Secretase Inhibitor?