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

Karen K. Hsiao, 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

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452 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 languageEnglish (US)
Pages (from-to)1203-1218
Number of pages16
JournalNeuron
Volume15
Issue number5
DOIs
StatePublished - Nov 1995

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hsiao, K. K., Borchelt, D. R., Olson, K., Johannsdottir, R., Kitt, C., Yunis, W., Xu, S., Eckman, C., Younkin, S., Price, D., Iadecola, C., Clark, H. B., & Carlson, G. (1995). Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron, 15(5), 1203-1218. https://doi.org/10.1016/0896-6273(95)90107-8