title: CD40 deficiency mitigates Alzheimer's disease pathology in transgenic mouse models.
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 signaling pathway is a potential therapeutic strategy in Alzheimer's disease.
authors.affiliation: The Roskamp Institute, Sarasota, FL 34243, USA. vlaporte@rfdn.org
authors.forename: Vincent
authors.initials: V
authors.lastname: Laporte
authors.forename: Ghania
authors.initials: G
authors.lastname: Ait-Ghezala
authors.forename: Claude-Henry
authors.initials: CH
authors.lastname: Volmar
authors.forename: Michael
authors.initials: M
authors.lastname: Mullan