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Microglial-derived extracellular vesicles (MDEVs) are emerging as important mediators of neuroimmune communication and potential biomarkers reflecting pathological processes occurring within the central nervous system (CNS). However, how EV-associated inflammatory signalling changes across different stages of AD remains poorly understood. In this study, we characterized the inflammatory molecular profile of serum-derived MDEVs in 22\n                    <jats:sc>AD<\/jats:sc>\n                    patients, 19 prodromal AD subjects, and 23 healthy controls (HC). Cytokine concentrations were also evaluated in paired serum and cerebrospinal fluid (CSF) samples to compare vesicle-associated and soluble inflammatory signals across biological compartments. MDEVs were isolated by size exclusion chromatography followed by TMEM119-based immunoenrichment. Cytokine quantification was performed using the Ella Simple Plex automated immunoassay platform. MDEVs from AD patients showed a generalized reduction in both pro- and anti-inflammatory cytokines compared to HC, including IL-1\u03b2, TNF-\u03b1, IL-2, IFN-\u03b3, IL-6, IL-12p70, IL-10, and IL-4. Notably, several alterations were already detectable at the prodromal stage. In contrast, soluble cytokines in serum and CSF displayed a predominantly pro-inflammatory profile in AD patients, with increased levels of IL-1\u03b2, TNF-\u03b1, and IL-12p70. No significant correlations were observed between cytokine levels measured in MDEVs and those detected in serum or CSF. Overall, these findings support the presence of a compartment-specific reorganization of inflammatory signalling during AD progression. Early alterations in MDEV inflammatory cargo may reflect disrupted EV-mediated neuroimmune communication and highlight the potential of MDEVs as accessible peripheral biomarkers of neuroinflammatory processes in AD.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02472-9","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:27:42Z","timestamp":1788514062000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microglia-derived extracellular vesicles uncover early alterations of inflammatory signaling in Alzheimer\u2019s disease"],"prefix":"10.1007","author":[{"given":"Chiara","family":"Bianchessi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Serpente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Ferri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Giudici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Arcaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Borracci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Visconte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Buccellato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Pintus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Arosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Arighi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fenoglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Galimberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"2472_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092133","author":"G Murdaca","year":"2022","unstructured":"Murdaca G, Paladin F, Casciaro M, Vicario CM, Gangemi S, Martino G. 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