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Progressive Cognitive Impairment and Anxiety Induction in the Absence of Plaque Deposition in C57BL/6 Inbred Mice Expressing Transgenic Amyloid Precursor Protein

Title
Progressive Cognitive Impairment and Anxiety Induction in the Absence of Plaque Deposition in C57BL/6 Inbred Mice Expressing Transgenic Amyloid Precursor Protein
Authors
Lee K.-W.Lee S.H.Kim H.Song J.-S.Yang S.-D.Paik S.G.Han P.-L.
Ewha Authors
한평림이강우
SCOPUS Author ID
한평림scopus
Issue Date
2004
Journal Title
Journal of Neuroscience Research
ISSN
0360-4012JCR Link
Citation
Journal of Neuroscience Research vol. 76, no. 4, pp. 572 - 580
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Numerous transgenic mouse models for Alzheimer's disease (AD) have been generated to recapitulate the histological pathogenesis and behavioral phenotypes of AD brain. However, none of the existing models exhibits the full spectrum of AD symptoms, nor have all of the traits mimicked by the developed animal models been successfully represented within a single mouse line, indicating that the development of transgenic lines showing new features of the AD-like brain should be explored. Here we report on a transgenic mouse line, named Tg-APP (Sw, V717F)/B6, that expresses the human amyloid precursor protein (APP) containing the Swedish and the V717F Indiana mutations in the brains of inbred C57BL/6 mice, designed to eliminate the potential phenotypic variations attributed to the compound genetic backgrounds adopted in most AD mouse models. The Tg-APP (Sw, V717F)/B6 mice expressed the transgene transcript, in the heterozygote state, at a level of 2.6 ± 0.1 fold higher than that of endogenous mouse APP. However, no Aβ-plaque deposition was produced in the brain of the Tg-APP (Sw, V717F)/B6 mice up to 18 months of age. The Tg-APP(Sw, V717F)/B6 mice at 13-15 months showed reduced expression of calbindin and c-Fos in the brain. The Tg-APP (Sw, V717F)/B6 mice at 11-14 months displayed decreased motor coordination, learning and memory deficits, and severely increased anxiety. These phenotypes were not observed in the Tg-APP (Sw, V717F)/B6 mice at 5-7 months. Microarray analysis revealed altered expression, in the amygdala of the Tg-APP (Sw, V717F)/B6 mice, of genes previously implicated in anxiety. Taken together, these results suggest that the transgenic APP, or its derivatives, produces the age-dependent pathophysiology of the AD-like brain and that the progressive cognitive impairment and anxiety induction can proceed in the absence of visible Aβ-plaque deposition. © 2004 Wiley-Liss, Inc.
DOI
10.1002/jnr.20127
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일반대학원 > 뇌·인지과학과 > Journal papers
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