Brain Res. 2004 Jul 23;1015(1-2):161-8.
Behavioral effects of
CD40-CD40L pathway disruption in aged PSAPP mice.
Todd Roach J, Volmar
CH, Dwivedi
S, Town T, Crescentini
R, Crawford F, Tan J, Mullan
M.
Roskamp Institute,
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.
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Keywords: CD40, CD40L, pathway, PSAPP, behavioral effects, Brain Res.