Emergence of synaptic and cognitive impairment in a mature-onset APP mouse model of Alzheimer's disease.

Acta Neuropathologica Communications
Sarmi SriMariana Vargas-Caballero

Abstract

The synaptic changes underlying the onset of cognitive impairment in Alzheimer's disease (AD) are poorly understood. In contrast to the well documented inhibition of long-term potentiation (LTP) in CA3-CA1 synapses by acute Aβ application in adult neurons from rodents, young amyloid precursor protein (APP) transgenic mouse models often, surprisingly, show normal LTP. This suggests that there may be important differences between mature-onset and developmental-onset APP expression/ Aβ accumulation and the ensuing synaptic and behavioural phenotype. Here, in agreement with previous studies, we observed that developmental expression of APPSw,Ind (3-4 month old mice from line 102, PLoS Med 2:e355, 2005), resulted in reduced basal synaptic transmission in CA3-CA1 synapses, normal LTP, impaired spatial working memory, but normal spatial reference memory. To analyse early Aβ-mediated synaptic dysfunction and cognitive impairment in a more mature brain, we used controllable mature-onset APPSw,Ind expression in line 102 mice. Within 3 weeks of mature-onset APPSw,Ind expression and Aβ accumulation, we detected the first synaptic dysfunction: an impairment of LTP in hippocampal CA3-CA1 synapses. Cognitively, at this time point, we observed...Continue Reading

References

Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·S FisherM L Oster-Granite
Jun 16, 1995·Science·B L Finlay, R B Darlington
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Dec 1, 1996·Brain : a Journal of Neurology·N C FoxM N Rossor
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·A Y HsiaL Mucke
Mar 21, 2000·Journal of Neuroscience Research·Q S ChenC W Xie
Jun 9, 2000·Annual Review of Neuroscience·S J MartinR G Morris
Jun 25, 2002·Neurobiology of Disease·E A AsanteJ Collinge
Sep 24, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ottavio V VitoloMichael Shelanski
Dec 7, 2002·Nature Neuroscience·Hiroki YasudaRobert C Malenka
Oct 8, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiao-Bo LiuEdward G Jones
Oct 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·Susanna B MierauOle Paulsen
Dec 21, 2004·Nature Neuroscience·James P ClearyKaren H Ashe
Jul 22, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniela PuzzoOttavio Arancio
Mar 21, 2006·Nature·David Stellwagen, Robert C Malenka
Apr 5, 2007·Nature Protocols·Robert M J Deacon, J Nicholas P Rawlins
Jul 27, 2007·Biological Psychiatry·Fortunato BattagliaRalph A Nixon
Jul 27, 2007·Neurobiology of Disease·M Paul MurphyJeffrey N Keller
Dec 28, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tracy L Young-PearseDennis J Selkoe
May 22, 2009·Journal of Neurochemistry·John Hardy
Sep 4, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zilai WangHui Zheng
Jan 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erik D RobersonLennart Mucke
Feb 4, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Olivia A ShiptonMariana Vargas-Caballero
Mar 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Allan WangJoanna L Jankowsky
Jan 31, 2012·Nature Neuroscience·Iryna BenilovaBart De Strooper
Mar 9, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Silvia A PurroPatricia C Salinas

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Citations

May 24, 2019·Science Translational Medicine·Elizabeth M C Fisher, David M Bannerman
Feb 2, 2020·Interdisciplinary Sciences, Computational Life Sciences·Fuzhang YangJiang Xie
Nov 16, 2019·Acta Neuropathologica Communications·Inès R H Ben-NejmaGeorgios A Keliris
Dec 10, 2019·Acta Neuropathologica Communications·Enrico FaldiniDetlef Balschun

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Methods Mentioned

BETA
transgenic
transgenics
dissection
Infrared Imaging
ELISA

Software Mentioned

Mesoscale
Ethovision

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