Antagonizing Il10 and Il4 signaling via intracerebral decoy receptor expression attenuates Aβ accumulation.

Multiple lines of evidence indicate that immune signaling can impact the pathological progression in Alzheimer's disease (AD), including amyloid deposition, tau aggregation, synaptic pathology and neurodegenerative trajectory. In earlier studies, we reported that intracerebral expression of the anti-inflammatory cytokines, Interleukin-10 (Il10) and Interleukin-4 (Il4), increased amyloid β (Aβ) burden in TgCRND8 mice, a preclinical model of AD-type amyloidosis. As both Interleukin-10 receptor (IL10R) and Interleukin-4 receptor (IL4R) are upregulated in an age-progressive manner in rodent models of AD and in specific regions of human AD brains, we hypothesized that a decoy receptor strategy specifically targeting Il10 and Il4 signaling could have a disease-modifying effect.

New mechanisms highlight the complex relationship of Apolipoprotein E and tau pathogenesis.

A rare variant of Apolipoprotein E3 with neuroprotective properties has been identified in autosomal-dominant Alzheimer's disease. In this issue of Neuron, Chen et al. show that direct interaction between this variant and tau blocks tau pathogenesis in rodent models.