Up-regulation of calsyntenin-3 by β-amyloid increases vulnerability of cortical neurons.

β-Amyloid (Aβ) may play an important role in the pathogenesis of Alzheimer's disease. However, a causal relationship between Aβ oligomers and layer-specific neurodegeneration has not been clarified. Here we show up-regulation of calsyntenin (Cst)-3 in cultured neurons treated with Aβ oligomers and in Tg2576 mice. Cst-3 is distributed in large neurons in layers 2-3 and 5 of the cerebral cortex, and accumulated in dystrophic neurites surrounding Aβ-plaques. Overexpression of Cst-3 accelerates neuronal death. These results indicate that up-regulation of Cst-3 in cortical neurons in layers 2-3 and 5 by Aβ oligomers may lead to increase in vulnerability of neurons.