Abstract
Much recent Alzheimer disease research has focused on the mechanism by which amyloid precursor protein is processed to form amyloid β-peptide. Now, a new study suggests that improper clearance of amyloid β-peptide may play just as large a part as amyloid β-peptide production in amyloid deposition (143–150).
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Selkoe, D.J. The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease. Trends. Cell Biol. 8, 447– 453 (1998).
Burdick, D. et al. Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J. Biol. Chem. 267 , 546–554 (1992).
Knauer, M.F. et al. Intracellular accumulation and resistance to degradation of the Alzheimer amyloid A4/beta protein. Proc. Natl. Acad. Sci. USA 89, 7437–7441 (( 1992).
Vassar, R. et al. β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735–741 (1999).
Wolfe, M.S. et al. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513–517 ( 1999).
Nordstedt, C. et al. The Alzheimer Aβ peptide develops protease resistance in association with its polymerization into fibrils. J. Biol. Chem. 269, 30773–30776 ( 1994).
Iwata, N. et al. Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition. Nature Med. 6, 143–150 (2000).
Small, D.H. The amyloid cascade hypothesis debate: emerging consensus on the role of Aβ and amyloid in Alzheimer's disease. The Sixth International Conference on Alzheimer's Disease (Amsterdam, The Netherlands) 5, 301–304, 1998.
Schenk, D. et al. Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173–177 (1999).
Irizarry, M.C. et al. Aβ deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J. Neurosci. 17, 7053–7059 (1997).
Calhoun, M.E. et al. Neuron loss in APP transgenic mice. Nature 395, 755–756 (1998).
Yang, A.J. et al. Intracellular Aβ 1-42 aggregates stimulate the accumulation of stable, insoluble amyloidogenic fragments of the amyloid precursor protein in transfected cells. J. Biol. Chem. 270, 14786–14792 (1995).
Skovronsky, D.M., Doms, R.W. & Lee, V.M. Detection of a novel intraneuronal pool of insoluble amyloid β protein that accumulates with time in culture. J. Cell Biol. 141, 1031–1039 (1998).
Lee, S.J. et al. A detergent-insoluble membrane compartment contains Aβ in vivo. Nature Med. 4, 730– 734 (1998).
Morishima-Kawashima, M. & Ihara, Y. The presence of amyloid β-protein in the detergent-insoluble membrane compartment of human neuroblastoma cells. Biochemistry 37, 15247–15253 (1998).
Welihinda, A.A., Tirasophon, W. & Kaufman, R.J. The cellular response to protein misfolding in the endoplasmic reticulum. Gene Express. 7, 293–300 (1999).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Glabe, C. Does Alzheimer disease tilt the scales of amyloid degradation versus accumulation?. Nat Med 6, 133–134 (2000). https://doi.org/10.1038/72215
Issue Date:
DOI: https://doi.org/10.1038/72215
This article is cited by
-
The main actors involved in parasitization of Heliothis virescens larva
Cell and Tissue Research (2012)
-
Estrogen Regulation of the Neprilysin Gene Through A Hormone-Responsive Element
Journal of Molecular Neuroscience (2009)
-
Aging-related Correlation of Insulin-degrading Enzyme with γ-Secretase-generated Products Involving Insulin and Glucose Levels in Transgenic Mice
Neurochemical Research (2005)
