N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits
N -truncated Aβ 4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ 4-42 rapidly forms aggregates possessing a high aggregatio...
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Veröffentlicht in: | Acta neuropathologica 2013-08, Vol.126 (2), p.189-205 |
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creator | Bouter, Yvonne Dietrich, Katharina Wittnam, Jessica L. Rezaei-Ghaleh, Nasrollah Pillot, Thierry Papot-Couturier, Sophie Lefebvre, Thomas Sprenger, Frederick Wirths, Oliver Zweckstetter, Markus Bayer, Thomas A. |
description | N
-truncated Aβ
4-42
is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ
4-42
rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ
4-42
is as toxic as pyroglutamate Aβ
3-42
and Aβ
1-42
. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ
4-42
, pyroglutamate Aβ
3-42
and Aβ
1-42
. Transgenic mice expressing Aβ
4-42
(Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ
4-42
correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that
N
-truncated Aβ
4-42
triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction. |
doi_str_mv | 10.1007/s00401-013-1129-2 |
format | Article |
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-truncated Aβ
4-42
is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ
4-42
rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ
4-42
is as toxic as pyroglutamate Aβ
3-42
and Aβ
1-42
. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ
4-42
, pyroglutamate Aβ
3-42
and Aβ
1-42
. Transgenic mice expressing Aβ
4-42
(Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ
4-42
correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that
N
-truncated Aβ
4-42
triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.</description><identifier>ISSN: 0001-6322</identifier><identifier>EISSN: 1432-0533</identifier><identifier>DOI: 10.1007/s00401-013-1129-2</identifier><identifier>PMID: 23685882</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Alzheimer Disease - etiology ; Alzheimer Disease - pathology ; Alzheimer's disease ; Amyloid - chemistry ; Amyloid - ultrastructure ; Amyloid beta-Peptides - chemistry ; Amyloid beta-Peptides - genetics ; Amyloid beta-Peptides - toxicity ; Amyloid beta-protein ; Animals ; Behavior, Animal - physiology ; Brain ; Female ; Fetus - cytology ; Genetic engineering ; Humans ; Injections, Intraventricular ; Male ; Maze Learning - physiology ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Electron, Transmission ; Molecular Weight ; Nerve Degeneration - etiology ; Nerve Degeneration - pathology ; Neurons - cytology ; Neurons - drug effects ; Neurons - pathology ; Neurosciences ; Original Paper ; Pathology ; Peptides ; Pregnancy ; Primary Cell Culture ; Rats ; Rats, Wistar ; Solubility ; Space Perception - physiology</subject><ispartof>Acta neuropathologica, 2013-08, Vol.126 (2), p.189-205</ispartof><rights>The Author(s) 2013</rights><rights>COPYRIGHT 2013 Springer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c542t-e296a2dce6cf5ff4c65f228c46da1459983b80b2c452f10d6d0d7a6ce081d9743</citedby><cites>FETCH-LOGICAL-c542t-e296a2dce6cf5ff4c65f228c46da1459983b80b2c452f10d6d0d7a6ce081d9743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00401-013-1129-2$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00401-013-1129-2$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23685882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bouter, Yvonne</creatorcontrib><creatorcontrib>Dietrich, Katharina</creatorcontrib><creatorcontrib>Wittnam, Jessica L.</creatorcontrib><creatorcontrib>Rezaei-Ghaleh, Nasrollah</creatorcontrib><creatorcontrib>Pillot, Thierry</creatorcontrib><creatorcontrib>Papot-Couturier, Sophie</creatorcontrib><creatorcontrib>Lefebvre, Thomas</creatorcontrib><creatorcontrib>Sprenger, Frederick</creatorcontrib><creatorcontrib>Wirths, Oliver</creatorcontrib><creatorcontrib>Zweckstetter, Markus</creatorcontrib><creatorcontrib>Bayer, Thomas A.</creatorcontrib><title>N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits</title><title>Acta neuropathologica</title><addtitle>Acta Neuropathol</addtitle><addtitle>Acta Neuropathol</addtitle><description>N
-truncated Aβ
4-42
is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ
4-42
rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ
4-42
is as toxic as pyroglutamate Aβ
3-42
and Aβ
1-42
. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ
4-42
, pyroglutamate Aβ
3-42
and Aβ
1-42
. Transgenic mice expressing Aβ
4-42
(Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ
4-42
correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that
N
-truncated Aβ
4-42
triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.</description><subject>Alzheimer Disease - etiology</subject><subject>Alzheimer Disease - pathology</subject><subject>Alzheimer's disease</subject><subject>Amyloid - chemistry</subject><subject>Amyloid - ultrastructure</subject><subject>Amyloid beta-Peptides - chemistry</subject><subject>Amyloid beta-Peptides - genetics</subject><subject>Amyloid beta-Peptides - toxicity</subject><subject>Amyloid beta-protein</subject><subject>Animals</subject><subject>Behavior, Animal - physiology</subject><subject>Brain</subject><subject>Female</subject><subject>Fetus - cytology</subject><subject>Genetic engineering</subject><subject>Humans</subject><subject>Injections, Intraventricular</subject><subject>Male</subject><subject>Maze Learning - physiology</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Electron, Transmission</subject><subject>Molecular Weight</subject><subject>Nerve Degeneration - etiology</subject><subject>Nerve Degeneration - pathology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - pathology</subject><subject>Neurosciences</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>Peptides</subject><subject>Pregnancy</subject><subject>Primary Cell Culture</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Solubility</subject><subject>Space Perception - physiology</subject><issn>0001-6322</issn><issn>1432-0533</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9ks1qFTEUx4Mo9nr1AdxIwE1dpCYnma-NcCn1A4pudB0y-ZimzCTXZKbQ1-qD9Jma67TFgkgWSc75_f-cnByE3jJ6wihtPmZKBWWEMk4Yg47AM7RhggOhFefP0YbSkq05wBF6lfNluUEjqpfoCHjdVm0LG7T_Tua0BK1ma7CarsfoDb69wce725sPWBAB2MU0ZZxn1Y8Wq2FIdih0xioY7INZ9OGsl9n-iYwxDGRUefZhwL29UFc-JjViY53Xfs6v0Qunxmzf3O9b9Ovz2c_Tr-T8x5dvp7tzoisBM7HQ1QqMtrV2lXNC15UDaLWojWKi6rqW9y3tQYsKHKOmNtQ0qtaWtsx0jeBb9Gn13S_9ZItRmEsZcp_8pNK1jMrLp5ngL-QQryRvAETp3xYd3xuk-HuxeZaTz9qOowo2LlkywTre8A6qgr5f0UGNVvrgYnHUB1zuuOC0Eq1oCnXyD6osYyevYygNKvEnArYKdIo5J-seq2dUHgZArgMgywDIwwBIKJp3fz_7UfHw4wWAFcglFQab5GVcUihf8R_XO7uJvCA</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Bouter, Yvonne</creator><creator>Dietrich, Katharina</creator><creator>Wittnam, Jessica L.</creator><creator>Rezaei-Ghaleh, Nasrollah</creator><creator>Pillot, Thierry</creator><creator>Papot-Couturier, Sophie</creator><creator>Lefebvre, Thomas</creator><creator>Sprenger, Frederick</creator><creator>Wirths, Oliver</creator><creator>Zweckstetter, Markus</creator><creator>Bayer, Thomas A.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20130801</creationdate><title>N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits</title><author>Bouter, Yvonne ; Dietrich, Katharina ; Wittnam, Jessica L. ; Rezaei-Ghaleh, Nasrollah ; Pillot, Thierry ; Papot-Couturier, Sophie ; Lefebvre, Thomas ; Sprenger, Frederick ; Wirths, Oliver ; Zweckstetter, Markus ; Bayer, Thomas A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c542t-e296a2dce6cf5ff4c65f228c46da1459983b80b2c452f10d6d0d7a6ce081d9743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Alzheimer Disease - etiology</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Amyloid - chemistry</topic><topic>Amyloid - ultrastructure</topic><topic>Amyloid beta-Peptides - chemistry</topic><topic>Amyloid beta-Peptides - genetics</topic><topic>Amyloid beta-Peptides - toxicity</topic><topic>Amyloid beta-protein</topic><topic>Animals</topic><topic>Behavior, Animal - physiology</topic><topic>Brain</topic><topic>Female</topic><topic>Fetus - cytology</topic><topic>Genetic engineering</topic><topic>Humans</topic><topic>Injections, Intraventricular</topic><topic>Male</topic><topic>Maze Learning - physiology</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Electron, Transmission</topic><topic>Molecular Weight</topic><topic>Nerve Degeneration - etiology</topic><topic>Nerve Degeneration - pathology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - pathology</topic><topic>Neurosciences</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Peptides</topic><topic>Pregnancy</topic><topic>Primary Cell Culture</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Solubility</topic><topic>Space Perception - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bouter, Yvonne</creatorcontrib><creatorcontrib>Dietrich, Katharina</creatorcontrib><creatorcontrib>Wittnam, Jessica L.</creatorcontrib><creatorcontrib>Rezaei-Ghaleh, Nasrollah</creatorcontrib><creatorcontrib>Pillot, Thierry</creatorcontrib><creatorcontrib>Papot-Couturier, Sophie</creatorcontrib><creatorcontrib>Lefebvre, Thomas</creatorcontrib><creatorcontrib>Sprenger, Frederick</creatorcontrib><creatorcontrib>Wirths, Oliver</creatorcontrib><creatorcontrib>Zweckstetter, Markus</creatorcontrib><creatorcontrib>Bayer, Thomas A.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta neuropathologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bouter, Yvonne</au><au>Dietrich, Katharina</au><au>Wittnam, Jessica L.</au><au>Rezaei-Ghaleh, Nasrollah</au><au>Pillot, Thierry</au><au>Papot-Couturier, Sophie</au><au>Lefebvre, Thomas</au><au>Sprenger, Frederick</au><au>Wirths, Oliver</au><au>Zweckstetter, Markus</au><au>Bayer, Thomas A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits</atitle><jtitle>Acta neuropathologica</jtitle><stitle>Acta Neuropathol</stitle><addtitle>Acta Neuropathol</addtitle><date>2013-08-01</date><risdate>2013</risdate><volume>126</volume><issue>2</issue><spage>189</spage><epage>205</epage><pages>189-205</pages><issn>0001-6322</issn><eissn>1432-0533</eissn><abstract>N
-truncated Aβ
4-42
is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ
4-42
rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ
4-42
is as toxic as pyroglutamate Aβ
3-42
and Aβ
1-42
. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ
4-42
, pyroglutamate Aβ
3-42
and Aβ
1-42
. Transgenic mice expressing Aβ
4-42
(Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ
4-42
correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that
N
-truncated Aβ
4-42
triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>23685882</pmid><doi>10.1007/s00401-013-1129-2</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record> |
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ispartof | Acta neuropathologica, 2013-08, Vol.126 (2), p.189-205 |
issn | 0001-6322 1432-0533 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3722453 |
source | MEDLINE; SpringerLink Journals - AutoHoldings |
subjects | Alzheimer Disease - etiology Alzheimer Disease - pathology Alzheimer's disease Amyloid - chemistry Amyloid - ultrastructure Amyloid beta-Peptides - chemistry Amyloid beta-Peptides - genetics Amyloid beta-Peptides - toxicity Amyloid beta-protein Animals Behavior, Animal - physiology Brain Female Fetus - cytology Genetic engineering Humans Injections, Intraventricular Male Maze Learning - physiology Medicine Medicine & Public Health Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Electron, Transmission Molecular Weight Nerve Degeneration - etiology Nerve Degeneration - pathology Neurons - cytology Neurons - drug effects Neurons - pathology Neurosciences Original Paper Pathology Peptides Pregnancy Primary Cell Culture Rats Rats, Wistar Solubility Space Perception - physiology |
title | N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits |
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