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Science 22 January 1993:
Vol. 259. no. 5094, pp. 514 - 516
DOI: 10.1126/science.8424174
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Articles

Science, Vol 259, Issue 5094, 514-516
Copyright © 1993 by American Association for the Advancement of Science

articles

Release of excess amyloid beta protein from a mutant amyloid beta protein precursor

XD Cai, TE Golde, and SG Younkin

Division of Neuropathology, Case Western Reserve University, Cleveland, OH 44106.

The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta.


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Interaction of Presenilins with the Filamin Family of Actin-Binding Proteins.
W. Zhang, S. W. Han, D. W. McKeel, A. Goate, and J. Y. Wu (1998)
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K. S. Ermekova, N. Zambrano, H. Linn, G. Minopoli, F. Gertler, T. Russo, and M. Sudol (1997)
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M. S. Forman, D. G. Cook, S. Leight, R. W. Doms, and V. M.-Y. Lee (1997)
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Slow Degradation of Aggregates of the Alzheimer's Disease Amyloid beta -Protein by Microglial Cells.
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J. Biol. Chem. 272, 7977-7982
   Abstract »    Full Text »    PDF »
The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta  protein ending at the 42nd (or 43rd) residue.
T. Tomita, K. Maruyama, T. C. Saido, H. Kume, K. Shinozaki, S. Tokuhiro, A. Capell, J. Walter, J. Grunberg, C. Haass, et al. (1997)
PNAS 94, 2025-2030
   Abstract »    Full Text »    PDF »
Amyloid precursor protein processing and Abeta 42 deposition in a transgenic mouse model of Alzheimer disease.
K. Johnson-Wood, M. Lee, R. Motter, K. Hu, G. Gordon, R. Barbour, K. Khan, M. Gordon, H. Tan, D. Games, et al. (1997)
PNAS 94, 1550-1555
   Abstract »    Full Text »    PDF »
Amyloid beta -Peptide Impairs Glucose Transport in Hippocampal and Cortical Neurons: Involvement of Membrane Lipid Peroxidation.
R. J. Mark, Z. Pang, J. W. Geddes, K. Uchida, and M. P. Mattson (1997)
J. Neurosci. 17, 1046-1054
   Abstract »    Full Text »    PDF »
Ectodomain Phosphorylation of beta -Amyloid Precursor Protein at Two Distinct Cellular Locations.
J. Walter, A. Capell, A. Y. Hung, H. Langen, M. Schnolzer, G. Thinakaran, S. S. Sisodia, D. J. Selkoe, and C. Haass (1997)
J. Biol. Chem. 272, 1896-1903
   Abstract »    Full Text »    PDF »
The Profile of Soluble Amyloid beta Protein in Cultured Cell Media. DETECTION AND QUANTIFICATION OF AMYLOID beta PROTEIN AND VARIANTS BY IMMUNOPRECIPITATION-MASS SPECTROMETRY.
R. Wang, D. Sweeney, S. E. Gandy, and S. S. Sisodia (1996)
J. Biol. Chem. 271, 31894-31902
   Abstract »    Full Text »    PDF »
beta -Secretase Processing of the beta -Amyloid Precursor Protein in Transgenic Mice Is Efficient in Neurons but Inefficient in Astrocytes.
J. Zhao, L. Paganini, L. Mucke, M. Gordon, L. Refolo, M. Carman, S. Sinha, T. Oltersdorf, I. Lieberburg, and L. McConlogue (1996)
J. Biol. Chem. 271, 31407-31411
   Abstract »    Full Text »    PDF »
Amyloid beta  Peptide of Alzheimer's Disease Downregulates Bcl-2 and Upregulates Bax Expression in Human Neurons.
E. Paradis, H. Douillard, M. Koutroumanis, C. Goodyer, and A. LeBlanc (1996)
J. Neurosci. 16, 7533-7539
   Abstract »    Full Text »    PDF »
The Alternatively Spliced Kunitz Protease Inhibitor Domain Alters Amyloid beta Protein Precursor Processing and Amyloid beta Protein Production in Cultured Cells.
L. Ho, K.-i. Fukuchi, and StevenG. Younkin (1996)
J. Biol. Chem. 271, 30929-30934
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The Carboxyl Termini of beta -Amyloid Peptides 1-40 and 1-42 Are Generated by Distinct gamma -Secretase Activities.
H.-W. Klafki, D. Abramowski, R. Swoboda, P.A. Paganetti, and M. Staufenbiel (1996)
J. Biol. Chem. 271, 28655-28659
   Abstract »    Full Text »    PDF »
Amyloidogenic Processing of Human Amyloid Precursor Protein in Hippocampal Neurons Devoid of Cathepsin D.
P. Saftig, C. Peters, K. von Figura, K. Craessaerts, F. Van Leuven, and B. De Strooper (1996)
J. Biol. Chem. 271, 27241-27244
   Abstract »    Full Text »    PDF »
Amyloid beta Peptide Formation in Cell-free Preparations. REGULATION BY PROTEIN KINASE C, CALMODULIN, AND CALCINEURIN.
F. Desdouits, J. D. Buxbaum, J. Desdouits-Magnen, AngusC. Nairn, and P. Greengard (1996)
J. Biol. Chem. 271, 24670-24674
   Abstract »    Full Text »    PDF »
Enhanced Amyloidogenic Processing of the beta -Amyloid Precursor Protein in Gene-targeted Mice Bearing the Swedish Familial Alzheimer's Disease Mutations and a ``Humanized'' Abeta Sequence.
A. G. Reaume, D. S. Howland, S. P. Trusko, M. J. Savage, D. M. Lang, B. D. Greenberg, R. Siman, and R. W. Scott (1996)
J. Biol. Chem. 271, 23380-23388
   Abstract »    Full Text »    PDF »
beta -Amyloid Precursor Protein. LOCATION OF TRANSMEMBRANE DOMAIN AND SPECIFICITY OF gamma -SECRETASE CLEAVAGE.
E. Tischer and B. Cordell (1996)
J. Biol. Chem. 271, 21914-21919
   Abstract »    Full Text »    PDF »
Amyloid beta -Protein and the Genetics of Alzheimer's Disease.
D. J. Selkoe and D. J. Selkoe (1996)
J. Biol. Chem. 271, 18295-18298
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Metabolism of the ``Swedish'' Amyloid Precursor Protein Variant in Neuro2a (N2a) Cells.
G. Thinakaran, D. B. Teplow, R. Siman, B. Greenberg, and S. S. Sisodia (1996)
J. Biol. Chem. 271, 9390-9397
   Abstract »    Full Text »    PDF »
Amyloids beta[IMAGE] and beta[IMAGE] Are Generated Intracellularly in Cultured Human Neurons and Their Secretion Increases with Maturation.
R. S. Turner, N. Suzuki, A. S. C. Chyung, S. G. Younkin, and V. M.-Y. Lee (1996)
J. Biol. Chem. 271, 8966-8970
   Abstract »    Full Text »    PDF »
Enhanced Release of Amyloid beta-Protein from Codon 670/671 ``Swedish'' Mutant beta-Amyloid Precursor Protein Occurs in Both Secretory and Endocytic Pathways.
R. G. Perez, S. L. Squazzo, and E. H. Koo (1996)
J. Biol. Chem. 271, 9100-9107
   Abstract »    Full Text »    PDF »
Degradation of Amyloid beta-Protein by a Serine Protease-alpha(2)-Macroglobulin Complex.
W. Q. Qiu, W. Borth, Z. Ye, C. Haass, D. B. Teplow, and D. J. Selkoe (1996)
J. Biol. Chem. 271, 8443-8451
   Abstract »    Full Text »    PDF »
Serotonin 5-HT2a and 5-HT2c Receptors Stimulate Amyloid Precursor Protein Ectodomain Secretion.
R. M. Nitsch, M. Deng, J. H. Growdon, and R. J. Wurtman (1996)
J. Biol. Chem. 271, 4188-4194
   Abstract »    Full Text »    PDF »
Differential Effects of a Rab6 Mutant on Secretory Versus Amyloidogenic Processing of Alzheimer's beta-Amyloid Precursor Protein.
L. McConlogue, F. Castellano, C. deWit, D. Schenk, and W. A. Maltese (1996)
J. Biol. Chem. 271, 1343-1348
   Abstract »    Full Text »    PDF »
Trafficking of cell-surface amyloid beta-protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization.
T Yamazaki, E. Koo, and D. Selkoe (1996)
J. Cell Sci. 109, 999-1008
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Neuronal Sorting and Processing of Amyloid Precursor Protein: Implications for Alzheimer's Disease.
P.J. Tienari, B. De Strooper, E. Ikonen, N. Ida, M. Simons, C.L. Masters, C.G. Dotti, and K. Beyreuther (1996)
Cold Spring Harb Symp Quant Biol 61, 575-585
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Cell Biology of the {beta}-Amyloid Precursor Protein and the Genetics of Alzheimer's Disease.
D.J. Selkoe (1996)
Cold Spring Harb Symp Quant Biol 61, 587-596
   Abstract »    PDF »
Neurodegenerative Diseases and Model Systems.
D.L. Price, D.R. Borchelt, P.C. Wong, C.A. Pardo, G. Thinakaran, M.K. Lee, D.W. Cleveland, and S.S. Sisodia (1996)
Cold Spring Harb Symp Quant Biol 61, 725-738
   Abstract »    PDF »


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