CD40 deficiency mitigates Alzheimer's disease pathology in transgenic mouse models

Journal of Neuroinflammation
Vincent LaporteMichael Mullan

Abstract

We have previously shown that transgenic mice carrying a mutant human APP but deficient in CD40L, display a decrease in astrocytosis and microgliosis associated with a lower amount of deposited Abeta. Furthermore, an anti-CD40L treatment causes a diminution of Abeta pathology in the brain and an improved performance in several cognitive tasks in the double transgenic PSAPP mouse model. Although these data suggest a potential role for CD40L in Alzheimer's disease pathology in transgenic mice they do not cast light on whether this effect is due to inhibition of signaling via CD40 or whether it is due to the mitigation of some other unknown role of CD40L. In the present report we have generated APP and PSAPP mouse models with a disrupted CD40 gene and compared the pathological features (such as amyloid burden, astrocytosis and microgliosis that are typical of Alzheimer's disease-like pathology in these transgenic mouse strains) with appropriate controls. We find that all these features are reduced in mouse models deficient for CD40 compared with their littermates where CD40 is present. These data suggest that CD40 signaling is required to allow the full repertoire of AD-like pathology in these mice and that inhibition of the CD40 ...Continue Reading

References

Feb 10, 1999·Experimental Gerontology·K Hsiao
Dec 2, 1999·Journal of Neuroimmunology·N Abdel-HaqW D Lyman
Mar 29, 2001·Physiological Reviews·D J Selkoe
Oct 12, 2001·Glia·Y Dong, E N Benveniste
Feb 16, 2002·The EMBO Journal·Jun TanMike Mullan
Oct 29, 2002·Nature Neuroscience·Jun TanMichael J Mullan
Jun 30, 2004·Brain Research·J Todd RoachMichael Mullan
Sep 27, 2005·Brain Research. Molecular Brain Research·Ghania Ait-GhezalaMike Mullan

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Citations

Feb 5, 2014·Journal of Neuroinflammation·Amy M BirchMagdalena Sastre
Aug 8, 2013·The International Journal of Neuroscience·M Obulesu, M Jhansilakshmi
Apr 17, 2007·The European Journal of Neuroscience·Ghania Ait-GhezalaMichael Mullan
May 11, 2015·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Róisín M McManusMarina A Lynch
Aug 24, 2019·Frontiers in Cellular Neuroscience·Saef IzzyMichael J Whalen
Jan 12, 2010·Brain, Behavior, and Immunity·K McQuillanKingston H G Mills

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Methods Mentioned

BETA
transgenic
genotyping
ELISA

Software Mentioned

Pro Plus
Image

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