The novel astrocytic marker CETN2 expression in Alzheimer’s disease

CETN2 is a centrosomal, calcium-binding protein implicated in mitosis and DNA repair best known for its expression in photoreceptors and ciliated cells. Here, we took advantage of a culture of human neuroepithelial stem (NES) to determine its expression in other cell types of the nervous tissue. We confirmed CETN2 centrosomal location in proliferating NES cells, and pointed out its relocation along with the differentiation process describing its cytoplasmic distribution in human astrocytes, while being absent in all other cell types. Next, we questioned about CETN2 role in pathologies in which aberrant calcium signaling and astrogliosis are part of the etiopathological process, finding in Alzheimer’s disease a prototypical condition. To this purpose, we examined CETN2 expression pattern in a cohort of control and sporadic AD patients investigating three brain areas differently hit by the disease: prefrontal and entorhinal cortices and the cerebellum.By immunoblot, stereological analysis, and targeted-mass spectrometry we report a positive correlation between entorhinal CETN2 immunoreactivity and the neurocognitive impairment, as well as with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. We also investigated the co-expression of CETN2 with STAT3, NFATc3 and YKL-40, known reactive glia markers, and their abundance in proximity to plaques of severely affected entorhinal cortices.Collectively our results provided not only the evidence that the novel astrocytic marker CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD, but also we identified CETN2 as an indicator of reactive astrogliosis.