Marine Bretou, Ragna Sannerud, Abril Escamilla-Ayala, Tom Leroy, Céline Vrancx, Zoë P Van Acker, Anika Perdok, Wendy Vermeire, Inge Vorsters, Sophie Van Keymolen, Michelle Maxson, Benjamin Pavie, Keimpe Wierda, Eeva-Liisa Eskelinen, Wim Annaert
Neuronal endosomal and lysosomal abnormalities are among the early changes observed in Alzheimer's disease (AD) before plaques appear. However, it is unclear whether distinct endolysosomal defects are temporally organized and how altered γ-secretase function or amyloid precursor protein (APP) metabolism contribute to these changes. Inhibiting γ-secretase chronically, in mouse embryonic fibroblast and hippocampal neurons, led to a gradual endolysosomal collapse initiated by decreased lysosomal calcium and increased cholesterol, causing downstream defects in endosomal recycling and maturation...
April 12, 2024: Developmental Cell