Behavioral effects of CD40-CD40L pathway disruption in aged PSAPP mice

Brain Research
J Todd RoachM Mullan

Abstract

We have shown that, when an amyloid-beta peptide (Abeta) overproducing transgenic mouse model (PSAPP) of Alzheimer's disease (AD) is treated with a depleting antibody against CD40L, it causes marked attenuation of Abeta pathology associated with decreased amyloidogenic processing of amyloid precursor protein (APP) and increased cerebral clearance of Abeta. Here, we report that, when PSAPP mice receive a regimen of anti-CD40L antibody commencing at an age associated with initial Abeta deposition, they demonstrate superior spatial memory on the standard water maze and radial arm water maze tasks, as well as exhibiting superior non-spatial memory in the object recognition test, as compared to control PSAPP mice. Furthermore, PSAPP mice treated with an anti-CD40L antibody regimen commencing at an age associated with extensive Abeta deposition demonstrate superior spatial memory on the standard water maze task, as compared to control PSAPP mice. Disruption of CD40L activity has beneficial effects on pathology and cognitive behavior in the PSAPP mouse model, providing support for the therapeutic potential of interrupting the CD40-CD40L interaction in AD.

References

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Citations

Jun 7, 2012·Amino Acids·Mauren Assis SouzaLuiz Fernando Freire Royes
Mar 1, 2006·Journal of Neuroinflammation·Vincent LaporteMichael Mullan
Oct 29, 2013·Journal of Neuroimmunology·Maria C O RodriguesSvitlana Garbuzova-Davis
Mar 29, 2013·Cellular and Molecular Life Sciences : CMLS·D RyanG Riedel
Aug 8, 2013·The International Journal of Neuroscience·M Obulesu, M Jhansilakshmi
Nov 12, 2009·Expert Review of Neurotherapeutics·Kavon Rezai-ZadehTerrence Town
Apr 19, 2011·European Journal of Pharmacology·Corbin BachmeierDaniel Paris
Mar 21, 2007·Neuroscience and Biobehavioral Reviews·Ekrem DereMaria A De Souza Silva
Sep 27, 2005·Brain Research. Molecular Brain Research·Ghania Ait-GhezalaMike Mullan
Jun 4, 2008·Neuro-degenerative Diseases·Jean-Christophe CasselJohn C Dalrymple-Alford
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Claude-Henry VolmarClaes Wahlestedt

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