Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice

Jean Cosme Dodart; Chantal Mathis; Josep Saura; Kelly R. Bales; Steven M. Paul; Arielle Ungerer

doi:10.1006/nbdi.1999.0278

Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice

Jean Cosme Dodart, Chantal Mathis, Josep Saura, Kelly R. Bales, Steven M. Paul, Arielle Ungerer

Washington University School of Medicine

Research output: Contribution to journal › Article › peer-review

109 Scopus citations

Abstract

Histological analyses were performed on the brains of APP(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APP(V717F) transgene and independent of amyloid deposition. (C) 2000 Academic Press.

Original language	English
Pages (from-to)	71-85
Number of pages	15
Journal	Neurobiology of Disease
Volume	7
Issue number	2
DOIs	https://doi.org/10.1006/nbdi.1999.0278
State	Published - Apr 2000

Keywords

APP
Alzheimer's disease
Amyloid precursor protein
Computer-assisted image analysis
Hippocampus
Immunohistochemistry
Synaptic density
Synaptophysin
Transgenic mice

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10.1006/nbdi.1999.0278

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title = "Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice",

abstract = "Histological analyses were performed on the brains of APP(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APP(V717F) transgene and independent of amyloid deposition. (C) 2000 Academic Press.",

keywords = "APP, Alzheimer's disease, Amyloid precursor protein, Computer-assisted image analysis, Hippocampus, Immunohistochemistry, Synaptic density, Synaptophysin, Transgenic mice",

author = "Dodart, {Jean Cosme} and Chantal Mathis and Josep Saura and Bales, {Kelly R.} and Paul, {Steven M.} and Arielle Ungerer",

note = "Funding Information: We are grateful to Drs. M. E. Stoeckel and M. J. Freund-Mercier (URA1446CNRS) for giving us access to and assistance with the fluorescence microscope. This work was supported by Eli Lilly Research & Company (Indianapolis, Indiana) and by a grant from the Association France Alzheimer (Paris, France).",

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AU - Paul, Steven M.

AU - Ungerer, Arielle

N1 - Funding Information: We are grateful to Drs. M. E. Stoeckel and M. J. Freund-Mercier (URA1446CNRS) for giving us access to and assistance with the fluorescence microscope. This work was supported by Eli Lilly Research & Company (Indianapolis, Indiana) and by a grant from the Association France Alzheimer (Paris, France).

PY - 2000/4

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N2 - Histological analyses were performed on the brains of APP(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APP(V717F) transgene and independent of amyloid deposition. (C) 2000 Academic Press.

AB - Histological analyses were performed on the brains of APP(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APP(V717F) transgene and independent of amyloid deposition. (C) 2000 Academic Press.

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KW - Transgenic mice

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Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice

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