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Commentary |
From the Departments of Psychiatry and Cell Biology, New York University School of Medicine, Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York
Abstract
Niemann-Pick Type C (NPC) is an inherited neurodegenerative disease of childhood and adolescence that develops from a failure of cholesterol trafficking within the endosomal-lysosomal pathway. Although NPC differs in major respects from Alzheimer’s disease (AD), intriguing parallels exist in the cellular pathology of these two diseases, including neurofibrillary tangle formation, prominent lysosome system dysfunction, and influences of apolipoprotein E 
4 genotype. Added to these similarities are new findings that some neuronal populations develop abnormalities of endosomes resembling those seen at the earliest stages of AD and also accumulate ß-cleaved amyloid precursor protein (APP) and Aß peptides within endosomes. In this commentary, the common features of endosome dysfunction are reviewed. Emerging evidence that endosome dysfunction may lead to ß-amyloidogenic APP processing or neurodegeneration by several different means is discussed.
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