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The disease is caused by mutations of either <jats:italic>NPC1<\/jats:italic> or <jats:italic>NPC2<\/jats:italic> gene and is accompanied by a severe loss of neurons in the cerebellum, but not in the hippocampus. NPC pathology exhibits some similarities with Alzheimer's disease, including increased levels of amyloid \u03b2 (A\u03b2)\u2010related peptides in vulnerable brain regions, but very little is known about the expression of amyloid precursor protein (APP) or APP secretases in NPC disease. In this article, we evaluated age\u2010related alterations in the level\/distribution of APP and its processing enzymes, \u03b2\u2010 and \u03b3\u2010secretases, in the hippocampus and cerebellum of <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, a well\u2010established model of NPC pathology. Our results show that levels and expression of APP and \u03b2\u2010secretase are elevated in the cerebellum prior to changes in the hippocampus, whereas \u03b3\u2010secretase components are enhanced in both brain regions at the same time in <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Interestingly, a subset of reactive astrocytes in <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mouse brains expresses high levels of APP as well as \u03b2\u2010 and \u03b3\u2010secretase components. Additionally, the activity of \u03b2\u2010secretase is enhanced in both the hippocampus and cerebellum of <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice at all ages, while the level of C\u2010terminal APP fragments is increased in the cerebellum of 10\u2010week\u2010old <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. These results, taken together, suggest that increased level and processing of APP may be associated with the development of pathology and\/or degenerative events observed in <jats:italic>Npc1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mouse brains. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.21001","type":"journal-article","created":{"date-parts":[[2010,4,21]],"date-time":"2010-04-21T18:26:49Z","timestamp":1271874409000},"page":"1267-1281","source":"Crossref","is-referenced-by-count":47,"title":["Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann\u2010Pick type C1\u2010deficient mouse brains"],"prefix":"10.1002","volume":"58","author":[{"given":"A.","family":"Kodam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maulik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Peake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Amritraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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