ArticleThe American journal of pathology2004
Intracellular accumulation of amyloidogenic fragments of amyloid-beta precursor protein in neurons with Niemann-Pick type C defects is associated with endosomal abnormalities.
Article in The American journal of pathology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 211 citations in OpenAlex.
- A multi-omics-empowered framework for precision diagnosis and treatment of lysosomal diseases.Journal of pharmaceutical analysis · 2025Review
- Biomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory Alignment.Journal of inherited metabolic disease · 2025Review
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Heterozygosity in NPC may be associated with neurologic and systemic phenotypes.Frontiers in neurology · 2025Review
- Maternal choline supplementation rescues early endosome pathology in basal forebrain cholinergic neurons in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.Neurobiology of aging · 2024Article
- Nitroxyl Hybrids with Curcumin and Stilbene Scaffolds Display Potent Antioxidant Activity, Remodel the Amyloid Beta Oligomer, and Reverse Amyloid Beta-Induced Cytotoxicity.Antioxidants (Basel, Switzerland) · 2024Article
- Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases.Nature reviews. Molecular cell biology · 2024Review
- Autophagy-lysosomal-associated neuronal death in neurodegenerative disease.Acta neuropathologica · 2024Review
- Accumulation of alkyl-lysophosphatidylcholines in Niemann-Pick disease type C1.Journal of lipid research · 2024Article
- Evaluation of the landscape of pharmacodynamic biomarkers in Niemann-Pick Disease Type C (NPC).Orphanet journal of rare diseases · 2024Review
- Potential Use of the Cholesterol Transfer Inhibitor U18666A as a Potent Research Tool for the Study of Cholesterol Mechanisms in Neurodegenerative Disorders.Molecular neurobiology · 2024Review
- Presenilin Deficiency Results in Cellular Cholesterol Accumulation by Impairment of Protein Glycosylation and NPC1 Function.International journal of molecular sciences · 2024Article
- Endosomal dysfunction contributes to cerebellar deficits in spinocerebellar ataxia type 6.eLife · 2023Article
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Review
- Lysosomal geneIBRO neuroscience reports · 2022Article
- Novel Stilbene-Nitroxyl Hybrid Compounds Display Discrete Modulation of Amyloid Beta Toxicity and Structure.Frontiers in chemistry · 2022Article
- A New Hypothesis for Alzheimer's Disease: The Lipid Invasion Model.Journal of Alzheimer's disease reports · 2022Article
- The CD22-IGF2R interaction is a therapeutic target for microglial lysosome dysfunction in Niemann-Pick type C.Science translational medicine · 2021Article
- Implications of exosomes derived from cholesterol-accumulated astrocytes in Alzheimer's disease pathology.Disease models & mechanisms · 2021Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niemann-Pick type C disease (NPC) is characterized by neurodegeneration secondary to impaired cholesterol trafficking and excessive glycosphingolipid storage. Abnormal cholesterol and ganglioside metabolism may influence the generation and aggregation of amyloidogenic fragments (ie, C99 and Abeta) from amyloid-beta precursor protein (APP), crucial factors causing neurodegeneration in Alzheimer's disease. To reveal whether abnormal accumulation and aggregation of APP fragments also occurs in NPC, we studied their expression in cultured cortical neurons treated with U18666A, a compound widely used to induce NPC defects, and also in brain tissues from NPC patients. U18666A treatment resulted in increased intraneuronal levels of C99 and insoluble Abeta42, which were distributed among early and late endosomes, in compartments distinct from where endogenous cholesterol accumulates. Analyses of NPC brains revealed that C99 or other APP C-terminal fragments (APP-CTF), but not Abeta42, accumulated in Purkinje cells, mainly in early endosomes. In contrast, in hippocampal pyramidal neurons, the major accumulated species was Abeta42, in late endosomes. Similar to what has been shown in Alzheimer's disease, cathepsin D, a lysosomal hydrolase, was redistributed to early endosomes in NPC Purkinje cells, where it co-localized with C99/APP-CTF. Our results suggest that endosomal abnormalities related to abnormal lipid trafficking in NPC may contribute to abnormal APP processing and Abeta42/C99/APP-CTF deposition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.