{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:13:15Z","timestamp":1789096395510,"version":"build-2803163510"},"reference-count":78,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2023,4,18]]},"abstract":"<jats:p>Background: Many transversal mechanisms act synergistically at different time-points in the cascade of Alzheimer\u2019s disease (AD), since amyloid-\u03b2 (A\u03b2) deposition, tau pathology, and neuroinflammation influence each other. Objective: We explored the contributions of microglia and astrocytes in patients with symptomatic sporadic AD stratified according to AT(N) system and APOE genotype. Methods: We compared the cerebrospinal fluid (CSF) levels of sTREM-2 and markers of astrocytic activation (GFAP; \u03b2-S100) from 71 patients with AD (23 A+T\u2013,48 A+T+; 38 APOE \u025b3, 33 APOE \u025b4) and 30 healthy controls (HC). With multivariate analyses we investigated associations between glial biomarkers, A\u03b242, and p-tau in all subgroups. Results: CSF sTREM-2 was higher in A+T+ [1.437 (0.264)] and A+T\u2013 [1.355 (0.213)] than in HC [1.042 (0.198); both p\u200a&lt;\u200a0.001]; GFAP and \u03b2-S100 were comparable across groups. Considering all patients, sTREM-2 positively associated with A\u03b242 (p\u200a=\u200a0.04) and p-tau (=0.016), with the first being present only in the A+T\u2013 subgroup (p\u200a=\u200a0.023). GFAP positively associated with A\u03b242 in all patients (p\u200a=\u200a0.020) and in the A+T+ subgroup (p\u200a=\u200a0.04). Stratifying by APOE, a positive association of sTREM-2 and p-tau was confirmed selectively in carriers of \u025b4 (p\u200a=\u200a0.018). Finally, sTREM-2 positively correlated with \u03b2-S100 in all subgroups, and with GFAP in A+T+ (p\u200a=\u200a0.042). Conclusion: Our results confirm the increase of CSF sTREM-2 in AD, which associates with reduced amyloidopathy in A+T\u2013 patients. Moreover, microglial activation seems to increase CSF tau levels in carriers of APOE \u025b4, is associated with astrocytic reactivity (GFAP) in A+T+, and likely leads the acquisition of a more neurotoxic astrocytic phenotype (\u03b2-S100).<\/jats:p>","DOI":"10.3233\/jad-221010","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T11:29:16Z","timestamp":1678188556000},"page":"1385-1397","source":"Crossref","is-referenced-by-count":19,"title":["Cerebrospinal Fluid sTREM-2, GFAP, and \u03b2-S100 in Symptomatic Sporadic Alzheimer\u2019s Disease: Microglial, Astrocytic, and APOE Contributions Along the Alzheimer\u2019s Disease Continuum"],"prefix":"10.1177","volume":"92","author":[{"given":"Chiara Giuseppina","family":"Bonomi","sequence":"first","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Assogna","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"},{"name":"Non Invasive Brain Stimulation Unit, IRCCS Santa Lucia, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Gaia","family":"Di Donna","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bernocchi","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Lucia","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Nuccetelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Fiorelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Loizzo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular, Endocrine-Metabolic and Ageing-Associated Diseases, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Neurology Unit, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Koch","sequence":"additional","affiliation":[{"name":"Non Invasive Brain Stimulation Unit, IRCCS Santa Lucia, Rome, Italy"},{"name":"Human Physiology Unit, Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Martorana","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Motta","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-221010_ref1","doi-asserted-by":"crossref","unstructured":"Brayne C , Miller B (2017) Dementia and aging populations-A global priority for contextualized research and health policy. 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