The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation.
Several pathogenic Alzheimer's disease (AD) mutations have been described, all of which cause increased amyloid beta-protein (Abeta) levels. Here we present studies of a pathogenic amyloid precursor protein (APP) mutation, located within the Abeta sequence at codon 693 (E693G), that causes AD i...
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2001
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ftcdlib:oai:escholarship.org/ark:/13030/qt2xp803q3 2023-05-15T14:44:34+02:00 The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nilsberth, C Westlind-Danielsson, A Eckman, CB Condron, MM Axelman, K Forsell, C Stenh, C Luthman, J Teplow, DB Younkin, SG Näslund, J Lannfelt, L 887 - 893 2001-09-01 application/pdf https://escholarship.org/uc/item/2xp803q3 unknown eScholarship, University of California qt2xp803q3 https://escholarship.org/uc/item/2xp803q3 public Nature neuroscience, vol 4, iss 9 Cell Line Humans Alzheimer Disease Peptide Fragments Amyloid beta-Protein Precursor Culture Media Pedigree Heterozygote Mutation Middle Aged Sweden Amyloid beta-Peptides Neurology & Neurosurgery Neurosciences Cognitive Sciences Psychology article 2001 ftcdlib 2019-12-20T23:54:42Z Several pathogenic Alzheimer's disease (AD) mutations have been described, all of which cause increased amyloid beta-protein (Abeta) levels. Here we present studies of a pathogenic amyloid precursor protein (APP) mutation, located within the Abeta sequence at codon 693 (E693G), that causes AD in a Swedish family. Carriers of this 'Arctic' mutation showed decreased Abeta42 and Abeta40 levels in plasma. Additionally, low levels of Abeta42 were detected in conditioned media from cells transfected with APPE693G. Fibrillization studies demonstrated no difference in fibrillization rate, but Abeta with the Arctic mutation formed protofibrils at a much higher rate and in larger quantities than wild-type (wt) Abeta. The finding of increased protofibril formation and decreased Abeta plasma levels in the Arctic AD may reflect an alternative pathogenic mechanism for AD involving rapid Abeta protofibril formation leading to accelerated buildup of insoluble Abeta intra- and/or extracellularly. Article in Journal/Newspaper Arctic University of California: eScholarship Arctic |
institution |
Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Cell Line Humans Alzheimer Disease Peptide Fragments Amyloid beta-Protein Precursor Culture Media Pedigree Heterozygote Mutation Middle Aged Sweden Amyloid beta-Peptides Neurology & Neurosurgery Neurosciences Cognitive Sciences Psychology |
spellingShingle |
Cell Line Humans Alzheimer Disease Peptide Fragments Amyloid beta-Protein Precursor Culture Media Pedigree Heterozygote Mutation Middle Aged Sweden Amyloid beta-Peptides Neurology & Neurosurgery Neurosciences Cognitive Sciences Psychology Nilsberth, C Westlind-Danielsson, A Eckman, CB Condron, MM Axelman, K Forsell, C Stenh, C Luthman, J Teplow, DB Younkin, SG Näslund, J Lannfelt, L The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. |
topic_facet |
Cell Line Humans Alzheimer Disease Peptide Fragments Amyloid beta-Protein Precursor Culture Media Pedigree Heterozygote Mutation Middle Aged Sweden Amyloid beta-Peptides Neurology & Neurosurgery Neurosciences Cognitive Sciences Psychology |
description |
Several pathogenic Alzheimer's disease (AD) mutations have been described, all of which cause increased amyloid beta-protein (Abeta) levels. Here we present studies of a pathogenic amyloid precursor protein (APP) mutation, located within the Abeta sequence at codon 693 (E693G), that causes AD in a Swedish family. Carriers of this 'Arctic' mutation showed decreased Abeta42 and Abeta40 levels in plasma. Additionally, low levels of Abeta42 were detected in conditioned media from cells transfected with APPE693G. Fibrillization studies demonstrated no difference in fibrillization rate, but Abeta with the Arctic mutation formed protofibrils at a much higher rate and in larger quantities than wild-type (wt) Abeta. The finding of increased protofibril formation and decreased Abeta plasma levels in the Arctic AD may reflect an alternative pathogenic mechanism for AD involving rapid Abeta protofibril formation leading to accelerated buildup of insoluble Abeta intra- and/or extracellularly. |
format |
Article in Journal/Newspaper |
author |
Nilsberth, C Westlind-Danielsson, A Eckman, CB Condron, MM Axelman, K Forsell, C Stenh, C Luthman, J Teplow, DB Younkin, SG Näslund, J Lannfelt, L |
author_facet |
Nilsberth, C Westlind-Danielsson, A Eckman, CB Condron, MM Axelman, K Forsell, C Stenh, C Luthman, J Teplow, DB Younkin, SG Näslund, J Lannfelt, L |
author_sort |
Nilsberth, C |
title |
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. |
title_short |
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. |
title_full |
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. |
title_fullStr |
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. |
title_full_unstemmed |
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. |
title_sort |
'arctic' app mutation (e693g) causes alzheimer's disease by enhanced abeta protofibril formation. |
publisher |
eScholarship, University of California |
publishDate |
2001 |
url |
https://escholarship.org/uc/item/2xp803q3 |
op_coverage |
887 - 893 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Nature neuroscience, vol 4, iss 9 |
op_relation |
qt2xp803q3 https://escholarship.org/uc/item/2xp803q3 |
op_rights |
public |
_version_ |
1766316050214813696 |