Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein
In Alzheimer's disease (AD), a progressive decline of cognitive functions is accompanied by neuropathology that includes the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature. We have proposed that a fragment of the Alzheimer amyloid precursor protei...
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| Veröffentlicht in: | Brain research. Molecular brain research. 1999-03, Vol.66 (1), p.150-162 |
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| container_title | Brain research. Molecular brain research. |
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| creator | Berger-Sweeney, Joanne McPhie, Donna L Arters, Jill A Greenan, Jane Oster-Granite, Mary Lou Neve, Rachael L |
| description | In Alzheimer's disease (AD), a progressive decline of cognitive functions is accompanied by neuropathology that includes the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature. We have proposed that a fragment of the Alzheimer amyloid precursor protein (APP) comprising the carboxyl-terminal 100 amino acids of this molecule (APP-C100) plays a crucial role in the neurodegeneration and subsequent cognitive decline in AD. To test this hypothesis, we performed behavioral analyses on transgenic mice expressing APP-C100 in the brain. The results revealed that homozygous APP-C100 transgenic mice were significantly impaired in cued, spatial and reversal performance of a Morris water maze task, that the degree of the impairment in the spatial learning was age-dependent, and that the homozygous mice displayed significantly more degeneration of neurons in Ammon's horn of the hippocampal formation than did heterozygous or control mice. Among the heterozygotes, females were relatively more impaired in their spatial learning than were males. These findings show that expression of APP-C100 in the brain can cause age-dependent cognitive impairments that are accompanied by hippocampal degeneration. |
| doi_str_mv | 10.1016/S0169-328X(99)00014-5 |
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We have proposed that a fragment of the Alzheimer amyloid precursor protein (APP) comprising the carboxyl-terminal 100 amino acids of this molecule (APP-C100) plays a crucial role in the neurodegeneration and subsequent cognitive decline in AD. To test this hypothesis, we performed behavioral analyses on transgenic mice expressing APP-C100 in the brain. The results revealed that homozygous APP-C100 transgenic mice were significantly impaired in cued, spatial and reversal performance of a Morris water maze task, that the degree of the impairment in the spatial learning was age-dependent, and that the homozygous mice displayed significantly more degeneration of neurons in Ammon's horn of the hippocampal formation than did heterozygous or control mice. Among the heterozygotes, females were relatively more impaired in their spatial learning than were males. These findings show that expression of APP-C100 in the brain can cause age-dependent cognitive impairments that are accompanied by hippocampal degeneration.</description><identifier>ISSN: 0169-328X</identifier><identifier>EISSN: 1872-6941</identifier><identifier>DOI: 10.1016/S0169-328X(99)00014-5</identifier><identifier>PMID: 10095087</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Age Factors ; Alzheimer disease ; Alzheimer Disease - genetics ; Amyloid beta-Protein Precursor - genetics ; Amyloid precursor protein ; Animals ; Behavior, Animal - physiology ; Biological and medical sciences ; Brain Chemistry - genetics ; Cognition ; Cognition - physiology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Female ; Gene ; Heterozygote ; Hippocampus - chemistry ; Hippocampus - physiology ; Homozygote ; Male ; Maze Learning - physiology ; Medical sciences ; Memory - physiology ; Mice ; Mice, Transgenic ; Mutagenesis - physiology ; Nerve Degeneration - genetics ; Neurodegeneration ; Neurology ; Neurotoxicity ; Sex Factors ; Space Perception - physiology ; Spatial learning ; Transgenes - physiology ; Transgenic mouse</subject><ispartof>Brain research. Molecular brain research., 1999-03, Vol.66 (1), p.150-162</ispartof><rights>1999 Elsevier Science B.V.</rights><rights>1999 INIST-CNRS</rights><rights>Copyright 1999 Elsevier Science B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-b08e9b3e2523c99a353800a67a8f0d5aca32c652f2d9cedd988225631e3443953</citedby><cites>FETCH-LOGICAL-c487t-b08e9b3e2523c99a353800a67a8f0d5aca32c652f2d9cedd988225631e3443953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1779261$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10095087$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berger-Sweeney, Joanne</creatorcontrib><creatorcontrib>McPhie, Donna L</creatorcontrib><creatorcontrib>Arters, Jill A</creatorcontrib><creatorcontrib>Greenan, Jane</creatorcontrib><creatorcontrib>Oster-Granite, Mary Lou</creatorcontrib><creatorcontrib>Neve, Rachael L</creatorcontrib><title>Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein</title><title>Brain research. Molecular brain research.</title><addtitle>Brain Res Mol Brain Res</addtitle><description>In Alzheimer's disease (AD), a progressive decline of cognitive functions is accompanied by neuropathology that includes the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature. We have proposed that a fragment of the Alzheimer amyloid precursor protein (APP) comprising the carboxyl-terminal 100 amino acids of this molecule (APP-C100) plays a crucial role in the neurodegeneration and subsequent cognitive decline in AD. To test this hypothesis, we performed behavioral analyses on transgenic mice expressing APP-C100 in the brain. The results revealed that homozygous APP-C100 transgenic mice were significantly impaired in cued, spatial and reversal performance of a Morris water maze task, that the degree of the impairment in the spatial learning was age-dependent, and that the homozygous mice displayed significantly more degeneration of neurons in Ammon's horn of the hippocampal formation than did heterozygous or control mice. Among the heterozygotes, females were relatively more impaired in their spatial learning than were males. These findings show that expression of APP-C100 in the brain can cause age-dependent cognitive impairments that are accompanied by hippocampal degeneration.</description><subject>Age Factors</subject><subject>Alzheimer disease</subject><subject>Alzheimer Disease - genetics</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid precursor protein</subject><subject>Animals</subject><subject>Behavior, Animal - physiology</subject><subject>Biological and medical sciences</subject><subject>Brain Chemistry - genetics</subject><subject>Cognition</subject><subject>Cognition - physiology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Female</subject><subject>Gene</subject><subject>Heterozygote</subject><subject>Hippocampus - chemistry</subject><subject>Hippocampus - physiology</subject><subject>Homozygote</subject><subject>Male</subject><subject>Maze Learning - physiology</subject><subject>Medical sciences</subject><subject>Memory - physiology</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Mutagenesis - physiology</subject><subject>Nerve Degeneration - genetics</subject><subject>Neurodegeneration</subject><subject>Neurology</subject><subject>Neurotoxicity</subject><subject>Sex Factors</subject><subject>Space Perception - physiology</subject><subject>Spatial learning</subject><subject>Transgenes - physiology</subject><subject>Transgenic mouse</subject><issn>0169-328X</issn><issn>1872-6941</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOFSEQhonROGdGH0HDwphx0cqlL7CamImXSSZxoSbuCA3VI6aBI9DGfgzfWPqcE3Xnhkrgq_qL_0foCSUvKaH9q4_1kA1n4sullC8IIbRtuntoR8XAml629D7a_UHO0HnO3zZIUPoQnVFCZEfEsEO_bvxeu-QhlIxdwDPoFFy4wzpY7MHHtGJtTKxUcGDxuOIAS4oW7iBA0sXFsPV5ZwCXpEOu987gKSZcvgI2Oo3x5zo3BZJ3Yck4TocH7dc5Oov3CcyScsX3KRZw4RF6MOk5w-NTvUCf3775dP2-uf3w7ub69W1jWjGUZiQC5MiBdYwbKTXvuCBE94MWE7GdNpoz03dsYlYasFYKwVjXcwq8bbns-AV6fpxbdb8vkIvyLhuYZx0gLlnRgQrZClbB7giaFHNOMKl9cl6nVVGitizUIQu1Ga2kVIcs1Cbw9CSwjB7sP11H8yvw7ATobPQ8VfeMy3-5YZCspxW7OmJQ3fjhIKlsHIT6KVe9K8pG959NfgN9lqmG</recordid><startdate>19990320</startdate><enddate>19990320</enddate><creator>Berger-Sweeney, Joanne</creator><creator>McPhie, Donna L</creator><creator>Arters, Jill A</creator><creator>Greenan, Jane</creator><creator>Oster-Granite, Mary Lou</creator><creator>Neve, Rachael L</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19990320</creationdate><title>Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein</title><author>Berger-Sweeney, Joanne ; McPhie, Donna L ; Arters, Jill A ; Greenan, Jane ; Oster-Granite, Mary Lou ; Neve, Rachael L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-b08e9b3e2523c99a353800a67a8f0d5aca32c652f2d9cedd988225631e3443953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Age Factors</topic><topic>Alzheimer disease</topic><topic>Alzheimer Disease - genetics</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid precursor protein</topic><topic>Animals</topic><topic>Behavior, Animal - physiology</topic><topic>Biological and medical sciences</topic><topic>Brain Chemistry - genetics</topic><topic>Cognition</topic><topic>Cognition - physiology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. 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Prion diseases</topic><topic>Female</topic><topic>Gene</topic><topic>Heterozygote</topic><topic>Hippocampus - chemistry</topic><topic>Hippocampus - physiology</topic><topic>Homozygote</topic><topic>Male</topic><topic>Maze Learning - physiology</topic><topic>Medical sciences</topic><topic>Memory - physiology</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Mutagenesis - physiology</topic><topic>Nerve Degeneration - genetics</topic><topic>Neurodegeneration</topic><topic>Neurology</topic><topic>Neurotoxicity</topic><topic>Sex Factors</topic><topic>Space Perception - physiology</topic><topic>Spatial learning</topic><topic>Transgenes - physiology</topic><topic>Transgenic mouse</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berger-Sweeney, Joanne</creatorcontrib><creatorcontrib>McPhie, Donna L</creatorcontrib><creatorcontrib>Arters, Jill A</creatorcontrib><creatorcontrib>Greenan, Jane</creatorcontrib><creatorcontrib>Oster-Granite, Mary Lou</creatorcontrib><creatorcontrib>Neve, Rachael L</creatorcontrib><collection>Pascal-Francis</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Brain research. Molecular brain research.</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berger-Sweeney, Joanne</au><au>McPhie, Donna L</au><au>Arters, Jill A</au><au>Greenan, Jane</au><au>Oster-Granite, Mary Lou</au><au>Neve, Rachael L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein</atitle><jtitle>Brain research. Molecular brain research.</jtitle><addtitle>Brain Res Mol Brain Res</addtitle><date>1999-03-20</date><risdate>1999</risdate><volume>66</volume><issue>1</issue><spage>150</spage><epage>162</epage><pages>150-162</pages><issn>0169-328X</issn><eissn>1872-6941</eissn><abstract>In Alzheimer's disease (AD), a progressive decline of cognitive functions is accompanied by neuropathology that includes the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature. We have proposed that a fragment of the Alzheimer amyloid precursor protein (APP) comprising the carboxyl-terminal 100 amino acids of this molecule (APP-C100) plays a crucial role in the neurodegeneration and subsequent cognitive decline in AD. To test this hypothesis, we performed behavioral analyses on transgenic mice expressing APP-C100 in the brain. The results revealed that homozygous APP-C100 transgenic mice were significantly impaired in cued, spatial and reversal performance of a Morris water maze task, that the degree of the impairment in the spatial learning was age-dependent, and that the homozygous mice displayed significantly more degeneration of neurons in Ammon's horn of the hippocampal formation than did heterozygous or control mice. Among the heterozygotes, females were relatively more impaired in their spatial learning than were males. These findings show that expression of APP-C100 in the brain can cause age-dependent cognitive impairments that are accompanied by hippocampal degeneration.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>10095087</pmid><doi>10.1016/S0169-328X(99)00014-5</doi><tpages>13</tpages></addata></record> |
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| subjects | Age Factors Alzheimer disease Alzheimer Disease - genetics Amyloid beta-Protein Precursor - genetics Amyloid precursor protein Animals Behavior, Animal - physiology Biological and medical sciences Brain Chemistry - genetics Cognition Cognition - physiology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female Gene Heterozygote Hippocampus - chemistry Hippocampus - physiology Homozygote Male Maze Learning - physiology Medical sciences Memory - physiology Mice Mice, Transgenic Mutagenesis - physiology Nerve Degeneration - genetics Neurodegeneration Neurology Neurotoxicity Sex Factors Space Perception - physiology Spatial learning Transgenes - physiology Transgenic mouse |
| title | Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein |
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