Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis

► Generation of NPC mice lacking APP, Appko/Npc1−/−. ► Loss of APP leads to deterioration of NPC disease phenotype. ► Appko/Npc1−/− mice display increased cholesterol, astrocytosis and tau abnormalities. ► Results consistent with dual pathway hypothesis of neurodegeneration in both AD and NPC