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In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium\u2010binding protein centrin\u20102 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted\u2010mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2\u2010positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL\u201040, indicating a human\u2010specific role in AD\u2010induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.<\/jats:p>","DOI":"10.1002\/glia.24603","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T07:40:21Z","timestamp":1723707621000},"page":"2158-2177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Astrocytic centrin\u20102 expression in entorhinal cortex correlates with\n                    <scp>Alzheimer's<\/scp>\n                    disease severity"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-0116","authenticated-orcid":false,"given":"Elisa","family":"Degl'Innocenti","sequence":"first","affiliation":[{"name":"Fondazione Pisana per la Scienza ONLUS  San Giuliano Terme Italy"},{"name":"Department of Translational 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