Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins

Karen H Ashe; David R. Borchelt; Kristine Olson; Rosa Johannsdottir; Cheryl Kitt; Wael Yunis; Sherry Xu; Chris Eckman; Steven Younkin; Donald Price; Costantino Iadecola; H. Brent Clark; George Carlson

doi:10.1016/0896-6273(95)90107-8

Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins

Karen H Ashe
, David R. Borchelt
, Kristine Olson
, Rosa Johannsdottir
, Cheryl Kitt
, Wael Yunis
, Sherry Xu
, Chris Eckman
, Steven Younkin
, Donald Price
, Costantino Iadecola
, H. Brent Clark
, George Carlson

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

498 Scopus citations

Abstract

Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP₆₉₅) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in ∼20% of nontransgenic mice when they reach mid-to late-adult life, suggesting that APP overexpression may accelerate a naturally occuring age-related CNS disorder in FVB/N mice.

Original language	English (US)
Pages (from-to)	1203-1218
Number of pages	16
Journal	Neuron
Volume	15
Issue number	5
DOIs	https://doi.org/10.1016/0896-6273(95)90107-8
State	Published - Nov 1995

Bibliographical note

Funding Information:
All correspondence should be addressed to K. K. H. The authors wish to thank Stanley B. Prusiner and Mike Scott for the hamster PrP cosmid vector; Robert Ehlenfeldt and Dallas Foster for generating transgenic mice; Jane Diedrich for valuable help and advice; Sangram Sisodia for providing APP cDNAs; Steven Nilsen, Jennifer Loh, Jim Meiners, Michael Guarnieri, and John Mojekwu for technical assistance; and David Knopman and Richard Price for support and encouragement. This work was supported by grants from the National Institutes of Health (AG07914, AG05146, and NS20471 to D. P. and D. R. B.; AG 10681 to G. C.; and NS33249 to K. H.), the Alzheimer's Association (K. K. H. and D. R. B.), the Culpeper Foundation (K. K. H.), and the Neurosciences Education and Research Foundation (K. K. H.).

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10.1016/0896-6273(95)90107-8

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@article{96e3e81d172c4e6b9ae6d0c69adbb406,

title = "Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins",

abstract = "Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in ∼20\% of nontransgenic mice when they reach mid-to late-adult life, suggesting that APP overexpression may accelerate a naturally occuring age-related CNS disorder in FVB/N mice.",

author = "Ashe, \{Karen H\} and Borchelt, \{David R.\} and Kristine Olson and Rosa Johannsdottir and Cheryl Kitt and Wael Yunis and Sherry Xu and Chris Eckman and Steven Younkin and Donald Price and Costantino Iadecola and Clark, \{H. Brent\} and George Carlson",

note = "Funding Information: All correspondence should be addressed to K. K. H. The authors wish to thank Stanley B. Prusiner and Mike Scott for the hamster PrP cosmid vector; Robert Ehlenfeldt and Dallas Foster for generating transgenic mice; Jane Diedrich for valuable help and advice; Sangram Sisodia for providing APP cDNAs; Steven Nilsen, Jennifer Loh, Jim Meiners, Michael Guarnieri, and John Mojekwu for technical assistance; and David Knopman and Richard Price for support and encouragement. This work was supported by grants from the National Institutes of Health (AG07914, AG05146, and NS20471 to D. P. and D. R. B.; AG 10681 to G. C.; and NS33249 to K. H.), the Alzheimer's Association (K. K. H. and D. R. B.), the Culpeper Foundation (K. K. H.), and the Neurosciences Education and Research Foundation (K. K. H.).",

year = "1995",

month = nov,

doi = "10.1016/0896-6273(95)90107-8",

language = "English (US)",

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pages = "1203--1218",

journal = "Neuron",

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T1 - Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins

AU - Ashe, Karen H

AU - Borchelt, David R.

AU - Olson, Kristine

AU - Johannsdottir, Rosa

AU - Kitt, Cheryl

AU - Yunis, Wael

AU - Xu, Sherry

AU - Eckman, Chris

AU - Younkin, Steven

AU - Price, Donald

AU - Iadecola, Costantino

AU - Clark, H. Brent

AU - Carlson, George

N1 - Funding Information: All correspondence should be addressed to K. K. H. The authors wish to thank Stanley B. Prusiner and Mike Scott for the hamster PrP cosmid vector; Robert Ehlenfeldt and Dallas Foster for generating transgenic mice; Jane Diedrich for valuable help and advice; Sangram Sisodia for providing APP cDNAs; Steven Nilsen, Jennifer Loh, Jim Meiners, Michael Guarnieri, and John Mojekwu for technical assistance; and David Knopman and Richard Price for support and encouragement. This work was supported by grants from the National Institutes of Health (AG07914, AG05146, and NS20471 to D. P. and D. R. B.; AG 10681 to G. C.; and NS33249 to K. H.), the Alzheimer's Association (K. K. H. and D. R. B.), the Culpeper Foundation (K. K. H.), and the Neurosciences Education and Research Foundation (K. K. H.).

PY - 1995/11

Y1 - 1995/11

N2 - Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in ∼20% of nontransgenic mice when they reach mid-to late-adult life, suggesting that APP overexpression may accelerate a naturally occuring age-related CNS disorder in FVB/N mice.

AB - Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP695) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levels of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. No extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in ∼20% of nontransgenic mice when they reach mid-to late-adult life, suggesting that APP overexpression may accelerate a naturally occuring age-related CNS disorder in FVB/N mice.

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Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins

Abstract

Bibliographical note

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