Abstract:Abstractγ‐Secretases are a family of intramembrane cleaving aspartyl proteases and important drug targets in Alzheimer's disease. Here, we generated mice deficient for all γ‐secretases in the pyramidal neurons of the postnatal forebrain by deleting the three anterior pharynx defective 1 (Aph1) subunits (Aph1abc cKO Cre
+). The mice show progressive cortical atrophy, neuronal loss, and gliosis. Interestingly, this is associated with more than 10‐fold accumulation of membrane‐bound fragments of App, Aplp1, Nrg1,…
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