The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons
Open accessAbstract
The amyloid precursor protein (APP) plays a crucial role in the pathogenesis of Alzheimer’s disease. During intracellular transport APP undergoes a series of proteolytic cleavages that lead to the release either of an amyloidogenic fragment called β-amyloid (Aβ) or of a nonamyloidogenic secreted form consisting of the ectodomain of APP (APP sec ). It is Aβ that accumulates in the brain lesions that are thought to cause the disease. By reducing the cellular cholesterol level of living hippocampal neurons by 70% with lovastatin and methyl-β-cyclodextrin, we show that the formation of Aβ is completely inhibited while the generation of APP sec is unperturbed. This inhibition of Aβ formation is accompanied by increased solubility in the detergent Triton X-100 and is fully reversible by the readdition of cholesterol to previously depleted cells. Our results show that cholesterol is required for Aβ formation to occur and imply a link between cholesterol, Aβ, and Alzheimer’s disease.
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Citations
Cites
Functional rafts in cell membranes
Simons, K., & Ikonen, E. (1997) · Nature · doi:10.1038/42408 · Cited by 9,757
Self-citationThe precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619
Self-citationREVIEWThe Gene Defects Responsible for Familial Alzheimer's Disease
Tanzi, R. E., Kovacs, D. M., Kim, T.-W., Moir, R. D., Guenette, S. Y., & Wasco, W. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0016 · Cited by 265
Cited by
Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
Linking lipids to Alzheimer's disease: cholesterol and beyond
Di Paolo, G., & Kim, T.-W. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3012 · Cited by 972
Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts
Ehehalt, R., Keller, P., Haass, C., Thiele, C., & Simons, K. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200207113 · Cited by 932
Self-citationLRP: a multifunctional scavenger and signaling receptor
Herz, J., & Strickland, D. K. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13992 · Cited by 908
Cholesterol metabolism in the brain
Dietschy, J. M., & Turley, S. D. (2001) · Current Opinion in Lipidology · doi:10.1097/00041433-200104000-00003 · Cited by 906
Metadata
- Authors
- Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., & Simons, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-05-26
- Volume
- 95
- Issue
- 11
- Pages
- 6460-6464
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1975806945
- Cited by
- 1,166
- References
- 3
- FWCI
- 24.09
- Type
- journal article
- Language
- en
- Open access
- green
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- Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C. G., & Simons, K. (1998). Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.11.6460
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