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Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides

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Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides. / Hartmann, T; Bieger, S C; Brühl, B; Tienari, P J; Ida, N; Allsop, D; Roberts, G W; Masters, C L; Dotti, C G; Unsicker, K; Beyreuther, K.

In: Nature Medicine, Vol. 3, No. 9, 09.1997, p. 1016-1020.

Research output: Contribution to journalJournal article

Harvard

Hartmann, T, Bieger, SC, Brühl, B, Tienari, PJ, Ida, N, Allsop, D, Roberts, GW, Masters, CL, Dotti, CG, Unsicker, K & Beyreuther, K 1997, 'Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides', Nature Medicine, vol. 3, no. 9, pp. 1016-1020. https://doi.org/10.1038/nm0997-1016

APA

Hartmann, T., Bieger, S. C., Brühl, B., Tienari, P. J., Ida, N., Allsop, D., ... Beyreuther, K. (1997). Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides. Nature Medicine, 3(9), 1016-1020. https://doi.org/10.1038/nm0997-1016

Vancouver

Hartmann T, Bieger SC, Brühl B, Tienari PJ, Ida N, Allsop D et al. Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides. Nature Medicine. 1997 Sep;3(9):1016-1020. https://doi.org/10.1038/nm0997-1016

Author

Hartmann, T ; Bieger, S C ; Brühl, B ; Tienari, P J ; Ida, N ; Allsop, D ; Roberts, G W ; Masters, C L ; Dotti, C G ; Unsicker, K ; Beyreuther, K. / Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides. In: Nature Medicine. 1997 ; Vol. 3, No. 9. pp. 1016-1020.

Bibtex

@article{3983500131784218bbf614ebbfa346a9,
title = "Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides",
abstract = "The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases, the most studied, but still unidentified ones, are those involved in the release of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma-secretase is the last processing step resulting in release of A beta. Cleavage occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42 [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus generally believed that inhibition of this enzyme could aid in prevention of AD. Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site for A beta(1-40) generation. It is interesting that intracellular generation of A beta seemed to be unique to neurons, because we found that nonneuronal cells produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell surface. The specific production of the critical A beta isoform in the ER of neurons links this compartment with the generation of A beta and explains why primarily ER localized (mutant) proteins such as the presenilins could induce AD. We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER.",
keywords = "Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Animals, Aspartic Acid Endopeptidases, COS Cells, Cell Compartmentation, Cell Membrane, Endopeptidases, Endoplasmic Reticulum, Golgi Apparatus, Hippocampus, Humans, Microscopy, Immunoelectron, Neurons, Peptide Fragments, Rats",
author = "T Hartmann and Bieger, {S C} and B Br{\"u}hl and Tienari, {P J} and N Ida and D Allsop and Roberts, {G W} and Masters, {C L} and Dotti, {C G} and K Unsicker and K Beyreuther",
year = "1997",
month = "9",
doi = "10.1038/nm0997-1016",
language = "English",
volume = "3",
pages = "1016--1020",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides

AU - Hartmann, T

AU - Bieger, S C

AU - Brühl, B

AU - Tienari, P J

AU - Ida, N

AU - Allsop, D

AU - Roberts, G W

AU - Masters, C L

AU - Dotti, C G

AU - Unsicker, K

AU - Beyreuther, K

PY - 1997/9

Y1 - 1997/9

N2 - The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases, the most studied, but still unidentified ones, are those involved in the release of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma-secretase is the last processing step resulting in release of A beta. Cleavage occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42 [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus generally believed that inhibition of this enzyme could aid in prevention of AD. Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site for A beta(1-40) generation. It is interesting that intracellular generation of A beta seemed to be unique to neurons, because we found that nonneuronal cells produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell surface. The specific production of the critical A beta isoform in the ER of neurons links this compartment with the generation of A beta and explains why primarily ER localized (mutant) proteins such as the presenilins could induce AD. We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER.

AB - The Alzheimer amyloid precursor protein (APP) is cleaved by several proteases, the most studied, but still unidentified ones, are those involved in the release of a fragment of APP, the amyloidogenic beta-protein A beta. Proteolysis by gamma-secretase is the last processing step resulting in release of A beta. Cleavage occurs after residue 40 of A beta [A beta(1-40)], occasionally after residue 42 [A beta(1-42)]. Even slightly increased amounts of this A beta(1-42) might be sufficient to cause Alzheimer's disease (AD) (reviewed in ref. 1, 2). It is thus generally believed that inhibition of this enzyme could aid in prevention of AD. Unexpectedly we have identified in neurons the endoplasmic reticulum (ER) as the site for generation of A beta(1-42) and the trans-Golgi network (TGN) as the site for A beta(1-40) generation. It is interesting that intracellular generation of A beta seemed to be unique to neurons, because we found that nonneuronal cells produced significant amounts of A beta(1-40) and A beta(1-42) only at the cell surface. The specific production of the critical A beta isoform in the ER of neurons links this compartment with the generation of A beta and explains why primarily ER localized (mutant) proteins such as the presenilins could induce AD. We suggest that the earliest event taking place in AD might be the generation of A beta(1-42) in the ER.

KW - Alzheimer Disease

KW - Amyloid Precursor Protein Secretases

KW - Amyloid beta-Peptides

KW - Animals

KW - Aspartic Acid Endopeptidases

KW - COS Cells

KW - Cell Compartmentation

KW - Cell Membrane

KW - Endopeptidases

KW - Endoplasmic Reticulum

KW - Golgi Apparatus

KW - Hippocampus

KW - Humans

KW - Microscopy, Immunoelectron

KW - Neurons

KW - Peptide Fragments

KW - Rats

U2 - 10.1038/nm0997-1016

DO - 10.1038/nm0997-1016

M3 - Journal article

C2 - 9288729

VL - 3

SP - 1016

EP - 1020

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 9

ER -