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Am J Pathol. 2004 Mar;164(3):757-61.

Niemann-Pick Type C disease and Alzheimer's disease: the APP-endosome connection fattens up.

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  • 1Department of Psychiatry, New York University School of Medicine, Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962, USA. Nixon@nki.rfmh.org

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 epsilon4 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 beta-cleaved amyloid precursor protein (APP) and Abeta peptides within endosomes. In this commentary, the common features of endosome dysfunction are reviewed. Emerging evidence that endosome dysfunction may lead to beta-amyloidogenic APP processing or neurodegeneration by several different means is discussed.

PMID:
14982829
[PubMed - indexed for MEDLINE]
PMCID:
PMC1613265
Free PMC Article
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