Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice
Oligomeric assemblies of amyloid‐β (Aβ) are suggested to be central in the pathogenesis of Alzheimer’s disease because levels of soluble Aβ correlate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover, such Aβ species have been shown to be neurotoxic, to int...
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crwiley:10.1111/j.1742-4658.2008.06836.x 2024-04-07T07:49:53+00:00 Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice Lord, Anna Englund, Hillevi Söderberg, Linda Tucker, Stina Clausen, Fredrik Hillered, Lars Gordon, Marcia Morgan, Dave Lannfelt, Lars Pettersson, Frida E. Nilsson, Lars N. G. 2009 http://dx.doi.org/10.1111/j.1742-4658.2008.06836.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1742-4658.2008.06836.x https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2008.06836.x en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor The FEBS Journal volume 276, issue 4, page 995-1006 ISSN 1742-464X 1742-4658 Cell Biology Molecular Biology Biochemistry journal-article 2009 crwiley https://doi.org/10.1111/j.1742-4658.2008.06836.x 2024-03-08T03:56:07Z Oligomeric assemblies of amyloid‐β (Aβ) are suggested to be central in the pathogenesis of Alzheimer’s disease because levels of soluble Aβ correlate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover, such Aβ species have been shown to be neurotoxic, to interfere with learned behavior and to inhibit the maintenance of hippocampal long‐term potentiation. The tg‐ArcSwe model (i.e. transgenic mice with the Arctic and Swedish Alzheimer mutations) expresses elevated levels of Aβ protofibrils in the brain, making tg‐ArcSwe a highly suitable model for investigating the pathogenic role of these Aβ assemblies. In the present study, we estimated Aβ protofibril levels in the brain and cerebrospinal fluid of tg‐ArcSwe mice, and also assessed their role with respect to cognitive functions. Protofibril levels, specifically measured with a sandwich ELISA, were found to be elevated in young tg‐ArcSwe mice compared to several transgenic models lacking the Arctic mutation. In aged tg‐ArcSwe mice with considerable plaque deposition, Aβ protofibrils were approximately 50% higher than in younger mice, whereas levels of total Aβ were exponentially increased. Young tg‐ArcSwe mice showed deficits in spatial learning, and individual performances in the Morris water maze were correlated inversely with levels of Aβ protofibrils, but not with total Aβ levels. We conclude that Aβ protofibrils accumulate in an age‐dependent manner in tg‐ArcSwe mice, although to a far lesser extent than total Aβ. Our findings suggest that increased levels of Aβ protofibrils could result in spatial learning impairment. Article in Journal/Newspaper Arctic Wiley Online Library Arctic FEBS Journal 276 4 995 1006 |
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Open Polar |
collection |
Wiley Online Library |
op_collection_id |
crwiley |
language |
English |
topic |
Cell Biology Molecular Biology Biochemistry |
spellingShingle |
Cell Biology Molecular Biology Biochemistry Lord, Anna Englund, Hillevi Söderberg, Linda Tucker, Stina Clausen, Fredrik Hillered, Lars Gordon, Marcia Morgan, Dave Lannfelt, Lars Pettersson, Frida E. Nilsson, Lars N. G. Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice |
topic_facet |
Cell Biology Molecular Biology Biochemistry |
description |
Oligomeric assemblies of amyloid‐β (Aβ) are suggested to be central in the pathogenesis of Alzheimer’s disease because levels of soluble Aβ correlate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover, such Aβ species have been shown to be neurotoxic, to interfere with learned behavior and to inhibit the maintenance of hippocampal long‐term potentiation. The tg‐ArcSwe model (i.e. transgenic mice with the Arctic and Swedish Alzheimer mutations) expresses elevated levels of Aβ protofibrils in the brain, making tg‐ArcSwe a highly suitable model for investigating the pathogenic role of these Aβ assemblies. In the present study, we estimated Aβ protofibril levels in the brain and cerebrospinal fluid of tg‐ArcSwe mice, and also assessed their role with respect to cognitive functions. Protofibril levels, specifically measured with a sandwich ELISA, were found to be elevated in young tg‐ArcSwe mice compared to several transgenic models lacking the Arctic mutation. In aged tg‐ArcSwe mice with considerable plaque deposition, Aβ protofibrils were approximately 50% higher than in younger mice, whereas levels of total Aβ were exponentially increased. Young tg‐ArcSwe mice showed deficits in spatial learning, and individual performances in the Morris water maze were correlated inversely with levels of Aβ protofibrils, but not with total Aβ levels. We conclude that Aβ protofibrils accumulate in an age‐dependent manner in tg‐ArcSwe mice, although to a far lesser extent than total Aβ. Our findings suggest that increased levels of Aβ protofibrils could result in spatial learning impairment. |
format |
Article in Journal/Newspaper |
author |
Lord, Anna Englund, Hillevi Söderberg, Linda Tucker, Stina Clausen, Fredrik Hillered, Lars Gordon, Marcia Morgan, Dave Lannfelt, Lars Pettersson, Frida E. Nilsson, Lars N. G. |
author_facet |
Lord, Anna Englund, Hillevi Söderberg, Linda Tucker, Stina Clausen, Fredrik Hillered, Lars Gordon, Marcia Morgan, Dave Lannfelt, Lars Pettersson, Frida E. Nilsson, Lars N. G. |
author_sort |
Lord, Anna |
title |
Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice |
title_short |
Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice |
title_full |
Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice |
title_fullStr |
Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice |
title_full_unstemmed |
Amyloid‐β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice |
title_sort |
amyloid‐β protofibril levels correlate with spatial learning in arctic alzheimer’s disease transgenic mice |
publisher |
Wiley |
publishDate |
2009 |
url |
http://dx.doi.org/10.1111/j.1742-4658.2008.06836.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1742-4658.2008.06836.x https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-4658.2008.06836.x |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
The FEBS Journal volume 276, issue 4, page 995-1006 ISSN 1742-464X 1742-4658 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1111/j.1742-4658.2008.06836.x |
container_title |
FEBS Journal |
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276 |
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4 |
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995 |
op_container_end_page |
1006 |
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1795664409509494784 |