Details

Autor(en) / Beteiligte

• Malnar, Martina
• Kosicek, Marko
• Mitterreiter, Stefan
• Omerbasic, Damir
• Lichtenthaler, Stefan F.
• Goate, Alison
• Hecimovic, Silva

Titel

Niemann–Pick type C cells show cholesterol dependent decrease of APP expression at the cell surface and its increased processing through the β-secretase pathway

Ist Teil von

• Biochimica et biophysica acta, 2010-07, Vol.1802 (7), p.682-691

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2010

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The link between cholesterol and Alzheimer's disease has recently been revealed in Niemann–Pick type C disease. We found that NPC1 − /− cells show decreased expression of APP at the cell surface and increased processing of APP through the β-secretase pathway resulting in increased C99, sAPPβ and intracellular Aβ40 levels. This effect is dependent on increased cholesterol levels, since cholesterol depletion reversed cell surface APP expression and lowered Aβ/C99 levels in NPC1 − / − cells to the levels observed in wt cells. Finding that overexpression of C99, a direct γ-secretase substrate, does not lead to increased intracellular Aβ levels in NPC1 − / − cells vs. CHOwt suggests that the effect on intracellular Aβ upon cholesterol accumulation in NPC1 − / − cells is not due to increased APP cleavage by γ-secretase. Our results indicate that cholesterol may modulate APP processing indirectly by modulating APP expression at the cell surface and thus its cleavage by β-secretase.