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Interestingly, this beneficial effect was without associated improvement of amyloid burden ( APP/PS1 /CB2R / mice ( APP/PS1 mice with additional CNR2 knockout) exhibited reduced levels of microglia, infiltrating macrophages, pro-inflammatory chemokines and cytokines, reduced soluble A (Schmle et al., 2015), and exacerbated cortical A deposition ( Conversely, reductions in CB1R have been detected in areas of microglial activation in brains of both people with AD and AD-relevant rodent models (Ramrez et al., 2005), and decreased levels of CB1R and AEA have also been found in A 42 -treated rats ( APP/PS1 /CB1R / mice ( APP/PS1 mice with additional CNR1 knockout) developed accelerated memory impairments in the two-object recognition test ( 42 levels and cognitive symptoms (Jung et al., 2012)